跳到主要內容

臺灣博碩士論文加值系統

(35.174.62.102) 您好!臺灣時間:2021/07/25 05:06
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:黃建彰
研究生(外文):Chien-Chang Huang
論文名稱:具高度演化保留之『頭對頭基因對』轉錄調控分析探討
論文名稱(外文):Study of the Transcriptional Regulation of Evolutionally Conserved Head-to-Head Gene Pairs
指導教授:張文祥張文祥引用關係
指導教授(外文):Wun-Shaing Wayne Chang
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2009
畢業學年度:98
語文別:中文
論文頁數:189
中文關鍵詞:雙向啟動子頭對頭基因對
外文關鍵詞:head-to-headbidirectional promoterPREPLC2ORF34
相關次數:
  • 被引用被引用:0
  • 點閱點閱:309
  • 評分評分:
  • 下載下載:47
  • 收藏至我的研究室書目清單書目收藏:0
原核生物可以有效率的藉由操縱元(operon)的獨特結構來調控一系列下游基因的轉錄及蛋白質合成,然而至目前為止卻尚未在真核生物的複雜基因系統中找到結構類似原核生物的操縱元結構。為了探討真核生物是否具有類似原核的操縱元結構來有效調控多個基因表現,我使用了人類及老鼠的基因體資訊作為研究基礎來檢測連續相鄰兩基因之間的重要性及關連性。根據基因在染色體上的轉錄方向,相鄰兩基因可以形成一個"基因對"並構成四種不同的組合:頭對頭 (head-to-head)、尾對尾(tail-to-tail)、頭對尾(head-to-tail)及尾對頭(tail-to-head)基因對。然而,令人驚訝的是在將所有基因排列分析後,將近有17.5%的頭對頭基因對以相鄰距離小於1000個核甘酸間距而廣泛的存在於人類基因體中。這一種的分佈情形僅明顯的存在於頭對頭基因對,並無在其他的基因對結構被觀察到。進一步的功能分析後更發現,參與特定功能的基因,像是DNA修補機制(DNA repair)或是氧化磷酸化系統(oxidative phosphorylation)的基因,大多以頭對頭的排列方式存在於基因體中,且其間的距離均小於300個核甘酸距離。這一些結果似乎暗示著高等生物的基因體中,為了有效的調控多基因的表現而以頭對頭的基因結構存在。為了更佳瞭解頭對頭基因在基因體中的調控方式,我個別的分離一個PREPL-C2ORF34基因對作為我的研究對象。北方墨點法檢測中發現此兩相鄰基因的表現呈現組織不對稱分佈情形,PREPL基因主要表現在腦與心臟組織,而C2ORF34幾乎在各個組織間都有表現。藉由啟動子序列分析發現PREPL與C2ORF34兩基因間距405個核甘酸長且帶有一個243個核甘酸長度的雙向調控因子(bidirectional promoter),可以有效的驅動PREPL與C2ORF34基因表現。此外深入研究更發現NRF-2與YY1兩個轉錄因子可以相互合作而有效的調控此雙向調控因子的活性。此外在肺臟轉錄調控研究中,發現PREPL基因轉錄調控可能而外藉由YY1來吸引组蛋白去乙醯酶(HDAC)而針對上游的調控區做乙醯化作用(acetylation)進而抑制PREPL在肺臟的表現活性。在這一系列的研究結果中,我推論在真核細胞中大量的存在著一種新的調控機制,此類的機制可以將許多功能性相近的基因(如DNA修補基因或是氧化磷酸化基因)以頭對頭的方式排列分佈在基因體中,並有效率的藉由基因對之間的雙向調控子來快速驅動。此外細胞亦同時的採用其他種調控機制(如乙醯化作用)來針對特定的基因(如PREPL)在特定的組織(如肺組織)或是環境下影響基因的表現程度而達成細胞能源節省及基因表現複雜度的雙贏局面。
It is well-known that genes in prokaryotes are arranged in short proximity and organized in an operonic architecture for effective co-expression and co-regulation. Corresponding studies in eukaryotes, however, no such operonic structure was found in complex loci of mammalian genomes. To examine whether there are similar operon-like organizations in mammalian genomes, I characterized and separated all the relative orientations of the human 35,306 and mouse 33,729 genes into four types of gene-pair organizations, defined as the nearest gene neighbors. Significantly, 17.5% of genes were found to be closely adjacent in a divergent manner with only less than 1,000-bp apart from each other, indicating that the head-to-head gene pairs are a common feature of mammalian genomes. Functionally, many of these head-to-head gene pairs were identified to participate in key physiological functions such as oxidative phosphorylation and DNA repair. Those findings suggested that the conserved head-to-head gene organizations, abundant in human and mouse genomes, contain an undiscovered exquisite mechanism to regulate series functional related genes based on the shared transcribed regions. The results also shed new insight to the novel bidirectional regulation in the complex loci of mammalian genomes. To more clarify the regulatory mechanism of bidirectional gene pair, I deeply investigate an evolutionarily conserved bidirectional gene pair, known as the PREPL-C2ORF34 gene pair. While PREPL is present primarily in brain and heart, C2ORF34 is ubiquitously and abundantly expressed in almost all tissues. Genomic analyses revealed that these two non-homologous genes are adjacent in a head-to-head configuration on human chromosome 2p21 and separated by only 405 bp. Within this short intergenic region, a 243-bp of GC-rich segment was demonstrated to function as a bidirectional minimal promoter to initiate the transcription of both flanking genes. Two key transcriptional factors, NRF-2 and YY1, were further identified to coordinately participate in driving both gene expressions in an additive manner. The functional cooperation between these two transcription factors, along with their genomic binding sites and some cis-acting repressive elements, are essential for the transcriptional activation and tissue distribution of the PREPL-C2ORF34 bidirectional gene pair. This study provides new insights into the complex transcriptional mechanism of an operon-like head-to-head organization in vertebrate and an exquisite bidirectional promoter for controlling the transcription of two adjacent genes.
CHAPTER 1 GENERAL INTRODUCTION
1.1 Prokaryotic Gene Regulation — Lac Operon as an Example……...…. 2
1.2 Operon-Like Transcription in Nematode Worms……………………… 3
1.3 Transcriptional Regulation in Mammalian Genomes……………..…... 5
1.4 Transcriptional Regulation of Two Neighboring Genes in
Eukaryotic Genomes……………………………………….……….......... 7
1.5 Regulatory Factors in Gene Expression and Transcription….……….. 10
1.5.1 Transcriptional Factors: NRF-2 and YY1………………………. 11
1.5.2 Histone Acetylation……………………………………………... 14
1.5.3 CpG Methylation…………………………………………........... 19
1.6 The PREPL-C2ORF34 Gene Pair — a Newly Identified
Evolutionally Conserved Head-to-Head Gene Pair………………….... 22

CHAPTER 2 MATERIALS AND METHODS
2.1 Databases Analysis…………………….…………………………….. ……27
2.1.1 Data Sources of Human and Mouse Genomes……………...……27
2.1.2 Identification and Classification of the Neighboring Genes…….. 27
2.1.3 Construction of the Orthologous Filter……………….……….... 28
2.1.4 Calculation of the Intergenic Distances of Two Consecutive Genes……………………………………………………………. 29
2.1.5 Analysis of the Conserved Linkage between Human and Mouse Genomes………………………………………………………… 29
2.1.6 Functional Characterization and Classification of Head-to-Head Gene Pairs……………………………..………………………. 30

2.2 Biochemical and Biological Analyses……………………………………. 31
2.2.1 Cell Cultures……………………………………………………. 31
2.2.2 Northern Blot Analysis……………………………………..…... 31
2.2.3 5’-Rapid Amplification of cDNA Ends (5’-RACE)……………. 32
2.2.4 Interspecies Comparison of the PREPL and C2ORF34 Genes.… 33
2.2.5 Bisulfite Sequencing Analysis of DNA Methylation………...… 34
2.2.6 Construction of Reporter Gene Plasmids…………………...…. 35
2.2.7 Transient Transfection and Dual Luciferase Reporter Assay….. 36
2.2.8 Preparation of Nuclear Proteins from Cultured Cells………..… 37
2.2.9 Electrophoretic Mobility Shift Assay (EMSA)…….…..……… 38
2.2.10 Reverse Transcription Polymerase Chain Reaction………….… 39
2.2.11 Chromatin Immunoprecipitation Assay……………………..…. 40
2.2.12 Knockdown of Endogenous NRF-2 and YY1 Transcriptional
Factors………………………………..……………………..….. 41
2.2.13 Western Blotting…………………………………...…………… 42

CHAPTER 3 GENOME-WIDE ANALYSIS OF THE ORENTATIONS OF GENE PAIRS AND THEIR INTERGENIC DISTANCES
3.1 Introduction…………………………………………..……..…………… 45
3.2 Results………………………………………………………..………….. 46
3.2.1 Study of the Distributions and Organizations of Consecutive
Gene Pairs in Human and Mouse Genomes…………………… 47
3.2.2 Characterization of the Gene-Pair Organization in Human and Mouse Genomes……………………….………………………. 54
3.2.3 Phylogenetic Analysis of the Consecutive Gene Pairs in Human and Mouse Genomes……………………………………...……. 58
3.2.4 Functional Classification of Head-to-Head Gene Pairs……...… 62
3.2.5 Identification and Characterization of Overlapping Gene
Pairs in Human and Mouse Genomes..………………..……….. 66
3.3 Discussion………………………………………………………..….……. 68

CHAPTER 4 TRANSCRIPTIONAL REGULATION OF EVOLUTIONALLY CONSERVED BIDIRECTIONAL GENE PAIRS: THE EXAMPLE OF PREPL-C2ORF34 HEAD-TO-HEAD GENE PAIRS
4.1 Introduction……………………………………………………..……….. 73
4.2 Results…..................................................................................................... 76
4.2.1 Identification of the PREPL-C2ORF34 Bidirectional
Gene Pair……………………………………………..………… 76
4.2.2 Tissue-Specific Expression Patterns of Human PREPL and
C2ORF34 Genes…..…..…………………………………....….. 78
4.2.3 Determination of the Size of the Intergenic Region between
Human C2ORF34 and PREPL Genes………………..……….… 80
4.2.4 Interspecies Comparison of the Gene Order, Orientation and Intergenic Spacing of the PREPL and C2ORF34 Genes………... 83
4.2.5 Functional Characterization of the Asymmetric Bidirectional
Promoter Activity of the Intergenic Region………………...…... 85
4.2.6 Identification of Transcription Factor Binding Sites in the Bidirectional Minimal Promoter…………………………… ….. 91
4.2.7 Characterization of the Specific NRF-2 and YY1 Transcription
Factors Binding to the Bidirectional Promoter by EMSA…….. 94
4.2.8 In vivo Occupancy of the Bidirectional Minimal Promoter
by Endogenous NRF-2 and YY1 Transcription Factors………. 101
4.2.9 NRF-2 and YY1 Are Essential for the Transcriptional
Activation of PREPL and C2ORF34 Genes............................... 103
4.2.10 HDAC1 is Localized to the PREPL Promoter Region………... 107
4.3 Discussion……………………………………………………………..… 110
CHAPTER 5 GENERAL DISCUSSION
5.1 Bidirectional Gene Pairs in Mammalian Genomes….…………… 116
5.2 Bidirectional Regulation of PREPL and C2ORF34……………… 120

APPENDIX…………………………………………………………………. 124
ABBREVIATIONS………………………………………………………… 144
REFERENCES…………………………………………………………….. 147
1.Reznikoff, W. S. (1972) The operon revisited, Annu Rev Genet 6, 133-156.
2.Gilbert, W., and Muller-Hill, B. (1966) Isolation of the Lac Repressor, Proc Natl Acad Sci U S A 56, 1891-1898.
3.Jacob, F., Perrin, D., Sanchez, C., and Monod, J. (1960) [Operon: a group of genes with the expression coordinated by an operator.], C R Hebd Seances Acad Sci 250, 1727-1729.
4.Ingraham, J. L., and Ingraham, C. A. (1995) Introduction to Microbiology.
5.Spieth, J., Brooke, G., Kuersten, S., Lea, K., and Blumenthal, T. (1993) Operons in C. elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions, Cell 73, 521-532.
6.Blumenthal, T., Evans, D., Link, C. D., Guffanti, A., Lawson, D., Thierry-Mieg, J., Thierry-Mieg, D., Chiu, W. L., Duke, K., Kiraly, M., and Kim, S. K. (2002) A global analysis of Caenorhabditis elegans operons, Nature 417, 851-854.
7.Zorio, D. A., Cheng, N. N., Blumenthal, T., and Spieth, J. (1994) Operons as a common form of chromosomal organization in C. elegans, Nature 372, 270-272.
8.Hannon, G. J., Maroney, P. A., and Nilsen, T. W. (1991) U small nuclear ribonucleoprotein requirements for nematode cis- and trans-splicing in vitro, J Biol Chem 266, 22792-22795.
9.Hastings, K. E. (2005) SL trans-splicing: easy come or easy go?, Trends Genet 21, 240-247.
10.Blumenthal, T. (2005) Trans-splicing and operons, WormBook, 1-9.
11.Blumenthal, T., and Gleason, K. S. (2003) Caenorhabditis elegans operons: form and function, Nat Rev Genet 4, 112-120.
12.McGinnis, W., and Krumlauf, R. (1992) Homeobox genes and axial patterning, Cell 68, 283-302.
13.Brooke, N. M., Garcia-Fernandez, J., and Holland, P. W. (1998) The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster, Nature 392, 920-922.
14.Jagla, K., Bellard, M., and Frasch, M. (2001) A cluster of Drosophila homeobox genes involved in mesoderm differentiation programs, Bioessays 23, 125-133.
15.Martinez, P., and Amemiya, C. T. (2002) Genomics of the HOX gene cluster, Comp Biochem Physiol B Biochem Mol Biol 133, 571-580.
16.Levings, P. P., and Bungert, J. (2002) The human beta-globin locus control region, Eur J Biochem 269, 1589-1599.
17.Tanimoto, K., Liu, Q., Bungert, J., and Engel, J. D. (1999) Effects of altered gene order or orientation of the locus control region on human beta-globin gene expression in mice, Nature 398, 344-348.
18.Forrester, W. C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1987) Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids, Nucleic Acids Res 15, 10159-10177.
19.Grosveld, F., van Assendelft, G. B., Greaves, D. R., and Kollias, G. (1987) Position-independent, high-level expression of the human beta-globin gene in transgenic mice, Cell 51, 975-985.
20.Bonifer, C. (2000) Developmental regulation of eukaryotic gene loci: which cis-regulatory information is required?, Trends Genet 16, 310-315.
21.Kruglyak, S., and Tang, H. (2000) Regulation of adjacent yeast genes, Trends Genet 16, 109-111.
22.Cohen, B. A., Mitra, R. D., Hughes, J. D., and Church, G. M. (2000) A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression, Nat Genet 26, 183-186.
23.Spellman, P. T., and Rubin, G. M. (2002) Evidence for large domains of similarly expressed genes in the Drosophila genome, J Biol 1, 5.
24.Boutanaev, A. M., Kalmykova, A. I., Shevelyov, Y. Y., and Nurminsky, D. I. (2002) Large clusters of co-expressed genes in the Drosophila genome, Nature 420, 666-669.
25.Mezey, J. G., Nuzhdin, S. V., Ye, F., and Jones, C. D. (2008) Coordinated evolution of co-expressed gene clusters in the Drosophila transcriptome, BMC Evol Biol 8, 2.
26.Lercher, M. J., Blumenthal, T., and Hurst, L. D. (2003) Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes, Genome Res 13, 238-243.
27.Miller, M. A., Cutter, A. D., Yamamoto, I., Ward, S., and Greenstein, D. (2004) Clustered organization of reproductive genes in the C. elegans genome, Curr Biol 14, 1284-1290.
28.Williams, E. J., and Bowles, D. J. (2004) Coexpression of neighboring genes in the genome of Arabidopsis thaliana, Genome Res 14, 1060-1067.
29.Zhan, S., Horrocks, J., and Lukens, L. N. (2006) Islands of co-expressed neighbouring genes in Arabidopsis thaliana suggest higher-order chromosome domains, Plant J 45, 347-357.
30.Poschl, E., Pollner, R., and Kuhn, K. (1988) The genes for the alpha 1(IV) and alpha 2(IV) chains of human basement membrane collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure, EMBO J 7, 2687-2695.
31.Hisano, M., Yamada, S., Tanaka, H., Nishimune, Y., and Nozaki, M. (2003) Genomic structure and promoter activity of the testis haploid germ cell-specific intronless genes, Tact1 and Tact2, Mol Reprod Dev 65, 148-156.
32.Dimitrov, S., Brennerova, M., and Forejt, J. (2001) Expression profiles and intergenic structure of head-to-head oriented Brca1 and Nbr1 genes, Gene 262, 89-98.
33.Hansen, J. J., Bross, P., Westergaard, M., Nielsen, M. N., Eiberg, H., Borglum, A. D., Mogensen, J., Kristiansen, K., Bolund, L., and Gregersen, N. (2003) Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter, Hum Genet 112, 71-77.
34.Yoshida, S., Harada, H., Nagai, H., Fukino, K., Teramoto, A., and Emi, M. (2002) Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene, J Hum Genet 47, 614-619.
35.Chinenov, Y., Coombs, C., and Martin, M. E. (2000) Isolation of a bi-directional promoter directing expression of the mouse GABPα and ATP synthase coupling factor 6 genes, Gene 261, 311-320.
36.Ma, J., and Ptashne, M. (1987) A new class of yeast transcriptional activators, Cell 51, 113-119.
37.Ptashne, M. (1988) How eukaryotic transcriptional activators work, Nature 335, 683-689.
38.Levine, M., and Manley, J. L. (1989) Transcriptional repression of eukaryotic promoters, Cell 59, 405-408.
39.Lin, Y. S., and Green, M. R. (1991) Mechanism of action of an acidic transcriptional activator in vitro, Cell 64, 971-981.
40.Madan Babu, M., and Teichmann, S. A. (2003) Functional determinants of transcription factors in Escherichia coli: protein families and binding sites, Trends Genet 19, 75-79.
41.Aerts, S., Thijs, G., Coessens, B., Staes, M., Moreau, Y., and De Moor, B. (2003) Toucan: deciphering the cis-regulatory logic of coregulated genes, Nucleic Acids Res 31, 1753-1764.
42.Lin, Y. S., Ha, I., Maldonado, E., Reinberg, D., and Green, M. R. (1991) Binding of general transcription factor TFIIB to an acidic activating region, Nature 353, 569-571.
43.Ptashne, M., and Gann, A. A. (1990) Activators and targets, Nature 346, 329-331.
44.Zhang, Y., and Reinberg, D. (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails, Genes Dev 15, 2343-2360.
45.Jaenisch, R., and Bird, A. (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals, Nat Genet 33 Suppl, 245-254.
46.Goll, M. G., and Bestor, T. H. (2005) Eukaryotic cytosine methyltransferases, Annu Rev Biochem 74, 481-514.
47.Kadonaga, J. T. (1990) Gene transcription: basal and regulated transcription by RNA polymerase II, Curr Opin Cell Biol 2, 496-501.
48.Saltzman, A. G., and Weinmann, R. (1989) Promoter specificity and modulation of RNA polymerase II transcription, FASEB J 3, 1723-1733.
49.Kim, K., Lecordier, A., and Bowman, L. H. (1995) Both nuclear and mitochondrial cytochrome c oxidase mRNA levels increase dramatically during mouse postnatal development, Biochem J 306 ( Pt 2), 353-358.
50.Ongwijitwat, S., Liang, H. L., Graboyes, E. M., and Wong-Riley, M. T. (2006) Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs, Gene 374, 39-49.
51.Scarpulla, R. C. (2002) Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells, Gene 286, 81-89.
52.Kelly, D. P., and Scarpulla, R. C. (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function, Genes Dev 18, 357-368.
53.Virbasius, J. V., and Scarpulla, R. C. (1991) Transcriptional activation through ETS domain binding sites in the cytochrome c oxidase subunit IV gene, Mol Cell Biol 11, 5631-5638.
54.Blesa, J. R., Prieto-Ruiz, J. A., Hernández, J. M., and Hernández-Yago, J. (2007) NRF-2 transcription factor is required for human TOMM20 gene expression, Gene 391, 198-208.
55.Delehouzee, S., Yoshikawa, T., Sawa, C., Sawada, J., Ito, T., Omori, M., Wada, T., Yamaguchi, Y., Kabe, Y., and Handa, H. (2005) GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis, Genes Cells 10, 717-731.
56.Savoysky, E., Mizuno, T., Sowa, Y., Watanabe, H., Sawada, J., Nomura, H., Ohsugi, Y., Handa, H., and Sakai, T. (1994) The retinoblastoma binding factor 1 (RBF-1) site in RB gene promoter binds preferentially E4TF1, a member of the Ets transcription factors family, Oncogene 9, 1839-1846.
57.Watanabe, H., Imai, T., Sharp, P. A., and Handa, H. (1988) Identification of two transcription factors that bind to specific elements in the promoter of the adenovirus early-region 4, Mol Cell Biol 8, 1290-1300.
58.Watanabe, H., Wada, T., and Handa, H. (1990) Transcription factor E4TF1 contains two subunits with different functions, EMBO J 9, 841-847.
59.Thompson, C. C., Brown, T. A., and McKnight, S. L. (1991) Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex, Science 253, 762-768.
60.Scarpulla, R. C. (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis, Biochim Biophys Acta 1576, 1-14.
61.Garesse, R., and Vallejo, C. G. (2001) Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes, Gene 263, 1-16.
62.Chinenov, Y., Henzl, M., and Martin, M. E. (2000) The alpha and beta subunits of the GA-binding protein form a stable heterodimer in solution. Revised model of heterotetrameric complex assembly, J Biol Chem 275, 7749-7756.
63.Virbasius, J. V., Virbasius, C. A., and Scarpulla, R. C. (1993) Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters, Genes Dev 7, 380-392.
64.Rosmarin, A. G., Resendes, K. K., Yang, Z., McMillan, J. N., and Fleming, S. L. (2004) GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein-protein interactions, Blood Cells Mol Dis 32, 143-154.
65.Martin, M. E., Piette, J., Yaniv, M., Tang, W. J., and Folk, W. R. (1988) Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins, Proc Natl Acad Sci U S A 85, 5839-5843.
66.Sawa, C., Goto, M., Suzuki, F., Watanabe, H., Sawada, J., and Handa, H. (1996) Functional domains of transcription factor hGABP beta1/E4TF1-53 required for nuclear localization and transcription activation, Nucleic Acids Res 24, 4954-4961.
67.LaMarco, K., Thompson, C. C., Byers, B. P., Walton, E. M., and McKnight, S. L. (1991) Identification of Ets- and notch-related subunits in GA binding protein, Science 253, 789-792.
68.Chrast, R., Chen, H., Morris, M. A., and Antonarakis, S. E. (1995) Mapping of the human transcription factor GABPA (E4TF1-60) gene to chromosome 21, Genomics 28, 119-122.
69.Patton, J., Block, S., Coombs, C., and Martin, M. E. (2006) Identification of functional elements in the murine Gabpα/ATP synthase coupling factor 6 bi-directional promoter, Gene 369, 35-44.
70.Sawa, C., Yoshikawa, T., Matsuda-Suzuki, F., Delehouzee, S., Goto, M., Watanabe, H., Sawada, J., Kataoka, K., and Handa, H. (2002) YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors, J Biol Chem 277, 22484-22490.
71.Donohoe, M. E., Zhang, X., McGinnis, L., Biggers, J., Li, E., and Shi, Y. (1999) Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality, Mol Cell Biol 19, 7237-7244.
72.Usheva, A., and Shenk, T. (1996) YY1 transcriptional initiator: protein interactions and association with a DNA site containing unpaired strands, Proc Natl Acad Sci U S A 93, 13571-13576.
73.Shi, Y., Seto, E., Chang, L. S., and Shenk, T. (1991) Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus E1A protein, Cell 67, 377-388.
74.Atchison, L., Ghias, A., Wilkinson, F., Bonini, N., and Atchison, M. L. (2003) Transcription factor YY1 functions as a PcG protein in vivo, EMBO J 22, 1347-1358.
75.Ficzycz, A., and Ovsenek, N. (2002) The Yin Yang 1 transcription factor associates with ribonucleoprotein (mRNP) complexes in the cytoplasm of Xenopus oocytes, J Biol Chem 277, 8382-8387.
76.Satijn, D. P., Hamer, K. M., den Blaauwen, J., and Otte, A. P. (2001) The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos, Mol Cell Biol 21, 1360-1369.
77.Seto, E., Lewis, B., and Shenk, T. (1993) Interaction between transcription factors Sp1 and YY1, Nature 365, 462-464.
78.Cole, E. G., and Gaston, K. (1997) A functional YY1 binding site is necessary and sufficient to activate Surf-1 promoter activity in response to serum growth factors, Nucleic Acids Res 25, 3705-3711.
79.Morgan, M. J., Woltering, J. M., In der Rieden, P. M., Durston, A. J., and Thiery, J. P. (2004) YY1 regulates the neural crest-associated slug gene in Xenopus laevis, J Biol Chem 279, 46826-46834.
80.Weill, L., Shestakova, E., and Bonnefoy, E. (2003) Transcription factor YY1 binds to the murine beta interferon promoter and regulates its transcriptional capacity with a dual activator/repressor role, J Virol 77, 2903-2914.
81.Coull, J. J., Romerio, F., Sun, J. M., Volker, J. L., Galvin, K. M., Davie, J. R., Shi, Y., Hansen, U., and Margolis, D. M. (2000) The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1, J Virol 74, 6790-6799.
82.Thomas, M. J., and Seto, E. (1999) Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key?, Gene 236, 197-208.
83.Yao, Y. L., Yang, W. M., and Seto, E. (2001) Regulation of transcription factor YY1 by acetylation and deacetylation, Mol Cell Biol 21, 5979-5991.
84.Flanagan, J. R., Becker, K. G., Ennist, D. L., Gleason, S. L., Driggers, P. H., Levi, B. Z., Appella, E., and Ozato, K. (1992) Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus, Mol Cell Biol 12, 38-44.
85.Shrivastava, A., and Calame, K. (1994) An analysis of genes regulated by the multi-functional transcriptional regulator Yin Yang-1, Nucleic Acids Res 22, 5151-5155.
86.Ye, J., Cippitelli, M., Dorman, L., Ortaldo, J. R., and Young, H. A. (1996) The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silencer element, Mol Cell Biol 16, 4744-4753.
87.Natesan, S., and Gilman, M. Z. (1993) DNA bending and orientation-dependent function of YY1 in the c-fos promoter, Genes Dev 7, 2497-2509.
88.Brown, J. L., Mucci, D., Whiteley, M., Dirksen, M. L., and Kassis, J. A. (1998) The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1, Mol Cell 1, 1057-1064.
89.Hariharan, N., Kelley, D. E., and Perry, R. P. (1991) Delta, a transcription factor that binds to downstream elements in several polymerase II promoters, is a functionally versatile zinc finger protein, Proc Natl Acad Sci U S A 88, 9799-9803.
90.Park, K., and Atchison, M. L. (1991) Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site, Proc Natl Acad Sci U S A 88, 9804-9808.
91.Pisaneschi, G., Ceccotti, S., Falchetti, M. L., Fiumicino, S., Carnevali, F., and Beccari, E. (1994) Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein binding to the first exon of L1 and L14 ribosomal protein genes, Biochem Biophys Res Commun 205, 1236-1242.
92.Austen, M., Luscher, B., and Luscher-Firzlaff, J. M. (1997) Characterization of the transcriptional regulator YY1. The bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein, J Biol Chem 272, 1709-1717.
93.Bushmeyer, S., Park, K., and Atchison, M. L. (1995) Characterization of functional domains within the multifunctional transcription factor, YY1, J Biol Chem 270, 30213-30220.
94.Bushmeyer, S. M., and Atchison, M. L. (1998) Identification of YY1 sequences necessary for association with the nuclear matrix and for transcriptional repression functions, J Cell Biochem 68, 484-499.
95.Lee, J. S., See, R. H., Galvin, K. M., Wang, J., and Shi, Y. (1995) Functional interactions between YY1 and adenovirus E1A, Nucleic Acids Res 23, 925-931.
96.Lee, T. C., Zhang, Y., and Schwartz, R. J. (1994) Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis, Oncogene 9, 1047-1052.
97.Lewis, B. A., Tullis, G., Seto, E., Horikoshi, N., Weinmann, R., and Shenk, T. (1995) Adenovirus E1A proteins interact with the cellular YY1 transcription factor, J Virol 69, 1628-1636.
98.Usheva, A., and Shenk, T. (1994) TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA, Cell 76, 1115-1121.
99.Lee, J. S., Galvin, K. M., and Shi, Y. (1993) Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1, Proc Natl Acad Sci U S A 90, 6145-6149.
100.Lee, J. S., Galvin, K. M., See, R. H., Eckner, R., Livingston, D., Moran, E., and Shi, Y. (1995) Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300, Genes Dev 9, 1188-1198.
101.Yang, W. M., Inouye, C., Zeng, Y., Bearss, D., and Seto, E. (1996) Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3, Proc Natl Acad Sci U S A 93, 12845-12850.
102.Yang, W. M., Yao, Y. L., Sun, J. M., Davie, J. R., and Seto, E. (1997) Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family, J Biol Chem 272, 28001-28007.
103.Gui, C. Y., and Dean, A. (2001) Acetylation of a specific promoter nucleosome accompanies activation of the epsilon-globin gene by beta-globin locus control region HS2, Mol Cell Biol 21, 1155-1163.
104.Santisteban, M. S., Arents, G., Moudrianakis, E. N., and Smith, M. M. (1997) Histone octamer function in vivo: mutations in the dimer-tetramer interfaces disrupt both gene activation and repression, EMBO J 16, 2493-2506.
105.Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F., and Richmond, T. J. (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution, Nature 389, 251-260.
106.Luger, K., and Richmond, T. J. (1998) The histone tails of the nucleosome, Curr Opin Genet Dev 8, 140-146.
107.Luger, K., and Richmond, T. J. (1998) DNA binding within the nucleosome core, Curr Opin Struct Biol 8, 33-40.
108.Protacio, R. U., Li, G., Lowary, P. T., and Widom, J. (2000) Effects of histone tail domains on the rate of transcriptional elongation through a nucleosome, Mol Cell Biol 20, 8866-8878.
109.Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B. D., Sun, Z. W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C. P., Allis, C. D., and Jenuwein, T. (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases, Nature 406, 593-599.
110.Grunstein, M. (1997) Histone acetylation in chromatin structure and transcription, Nature 389, 349-352.
111.Jasencakova, Z., Meister, A., Walter, J., Turner, B. M., and Schubert, I. (2000) Histone H4 acetylation of euchromatin and heterochromatin is cell cycle dependent and correlated with replication rather than with transcription, Plant Cell 12, 2087-2100.
112.Sterner, D. E., and Berger, S. L. (2000) Acetylation of histones and transcription-related factors, Microbiol Mol Biol Rev 64, 435-459.
113.Turner, B. M. (2000) Histone acetylation and an epigenetic code, Bioessays 22, 836-845.
114.Cheung, P., Tanner, K. G., Cheung, W. L., Sassone-Corsi, P., Denu, J. M., and Allis, C. D. (2000) Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation, Mol Cell 5, 905-915.
115.Emiliani, S., Fischle, W., Van Lint, C., Al-Abed, Y., and Verdin, E. (1998) Characterization of a human RPD3 ortholog, HDAC3, Proc Natl Acad Sci U S A 95, 2795-2800.
116.Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G. F., Johanson, K., Sung, C. M., Liu, R., and Winkler, J. (2000) Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor, J Biol Chem 275, 15254-15264.
117.Taunton, J., Hassig, C. A., and Schreiber, S. L. (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p, Science 272, 408-411.
118.Chen, H., Lin, R. J., Xie, W., Wilpitz, D., and Evans, R. M. (1999) Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase, Cell 98, 675-686.
119.McBlane, F., and Boyes, J. (2000) Stimulation of V(D)J recombination by histone acetylation, Curr Biol 10, 483-486.
120.Kim, M. S., Kwon, H. J., Lee, Y. M., Baek, J. H., Jang, J. E., Lee, S. W., Moon, E. J., Kim, H. S., Lee, S. K., Chung, H. Y., Kim, C. W., and Kim, K. W. (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes, Nat Med 7, 437-443.
121.Tai, K. Y., Shiah, S. G., Shieh, Y. S., Kao, Y. R., Chi, C. Y., Huang, E., Lee, H. S., Chang, L. C., Yang, P. C., and Wu, C. W. (2007) DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression, Oncogene 26, 3989-3997.
122.Ito, K., Barnes, P. J., and Adcock, I. M. (2000) Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12, Mol Cell Biol 20, 6891-6903.
123.Kadosh, D., and Struhl, K. (1997) Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters, Cell 89, 365-371.
124.Bhalla, K. N. (2005) Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies, J Clin Oncol 23, 3971-3993.
125.Blander, G., and Guarente, L. (2004) The Sir2 family of protein deacetylases, Annu Rev Biochem 73, 417-435.
126.Dokmanovic, M., Clarke, C., and Marks, P. A. (2007) Histone deacetylase inhibitors: overview and perspectives, Mol Cancer Res 5, 981-989.
127.Marks, P. A., and Dokmanovic, M. (2005) Histone deacetylase inhibitors: discovery and development as anticancer agents, Expert Opin Investig Drugs 14, 1497-1511.
128.Xu, W. S., Parmigiani, R. B., and Marks, P. A. (2007) Histone deacetylase inhibitors: molecular mechanisms of action, Oncogene 26, 5541-5552.
129.Sauve, A. A., Wolberger, C., Schramm, V. L., and Boeke, J. D. (2006) The biochemistry of sirtuins, Annu Rev Biochem 75, 435-465.
130.Vanommeslaeghe, K., Van Alsenoy, C., De Proft, F., Martins, J. C., Tourwe, D., and Geerlings, P. (2003) Ab initio study of the binding of Trichostatin A (TSA) in the active site of histone deacetylase like protein (HDLP), Org Biomol Chem 1, 2951-2957.
131.Finnin, M. S., Donigian, J. R., Cohen, A., Richon, V. M., Rifkind, R. A., Marks, P. A., Breslow, R., and Pavletich, N. P. (1999) Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors, Nature 401, 188-193.
132.Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., Chakravarty, P., Paolini, C., De Francesco, R., Gallinari, P., Steinkuhler, C., and Di Marco, S. (2004) Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor, Proc Natl Acad Sci U S A 101, 15064-15069.
133.Simonsson, S., and Gurdon, J. (2004) DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei, Nat Cell Biol 6, 984-990.
134.Newell-Price, J., Clark, A. J., and King, P. (2000) DNA methylation and silencing of gene expression, Trends Endocrinol Metab 11, 142-148.
135.Robertson, K. D. (2001) DNA methylation, methyltransferases, and cancer, Oncogene 20, 3139-3155.
136.Bestor, T. H. (1988) Cloning of a mammalian DNA methyltransferase, Gene 74, 9-12.
137.Okano, M., Xie, S., and Li, E. (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases, Nat Genet 19, 219-220.
138.Gardiner-Garden, M., and Frommer, M. (1987) CpG islands in vertebrate genomes, J Mol Biol 196, 261-282.
139.Trinklein, N. D., Aldred, S. F., Hartman, S. J., Schroeder, D. I., Otillar, R. P., and Myers, R. M. (2004) An abundance of bidirectional promoters in the human genome, Genome Res 14, 62-66.
140.Ropke, A., Buhtz, P., Bohm, M., Seger, J., Wieland, I., Allhoff, E. P., and Wieacker, P. F. (2005) Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer, Oncogene 24, 6667-6675.
141.Agirre, X., Roman-Gomez, J., Vazquez, I., Jimenez-Velasco, A., Garate, L., Montiel-Duarte, C., Artieda, P., Cordeu, L., Lahortiga, I., Calasanz, M. J., Heiniger, A., Torres, A., Minna, J. D., and Prosper, F. (2006) Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia, Int J Cancer 118, 1945-1953.
142.Takai, D., and Jones, P. A. (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22, Proc Natl Acad Sci U S A 99, 3740-3745.
143.Takai, D., and Jones, P. A. (2004) Origins of bidirectional promoters: computational analyses of intergenic distance in the human genome, Mol Biol Evol 21, 463-467.
144.Shu, J., Jelinek, J., Chang, H., Shen, L., Qin, T., Chung, W., Oki, Y., and Issa, J. P. (2006) Silencing of bidirectional promoters by DNA methylation in tumorigenesis, Cancer Res 66, 5077-5084.
145.Asakawa, S., Tsunematsu, K., Takayanagi, A., Sasaki, T., Shimizu, A., Shintani, A., Kawasaki, K., Mungall, A. J., Beck, S., Minoshima, S., and Shimizu, N. (2001) The genomic structure and promoter region of the human parkin gene, Biochem Biophys Res Commun 286, 863-868.
146.West, A. B., Lockhart, P. J., O'Farell, C., and Farrer, M. J. (2003) Identification of a novel gene linked to parkin via a bi-directional promoter, J Mol Biol 326, 11-19.
147.Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1997) Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro, DNA Res 4, 307-313.
148.Parvari, R., Gonen, Y., Alshafee, I., Buriakovsky, S., Regev, K., and Hershkovitz, E. (2005) The 2p21 deletion syndrome: Characterization of the transcription content, Genomics 86, 195-211.
149.Szeltner, Z., Alshafee, I., Juhasz, T., Parvari, R., and Polgar, L. (2005) The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity, Cell Mol Life Sci 62, 2376-2381.
150.Polgar, L. (2002) The prolyl oligopeptidase family, Cell Mol Life Sci 59, 349-362.
151.Calonge, M. J., Gasparini, P., Chillaron, J., Chillon, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccola, B., Di Silverio, F., and et al. (1994) Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine, Nat Genet 6, 420-425.
152.Parvari, R., Brodyansky, I., Elpeleg, O., Moses, S., Landau, D., and Hershkovitz, E. (2001) A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease, Am J Hum Genet 69, 869-875.
153.Jaeken, J., Martens, K., Francois, I., Eyskens, F., Lecointre, C., Derua, R., Meulemans, S., Slootstra, J. W., Waelkens, E., de Zegher, F., Creemers, J. W., and Matthijs, G. (2006) Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome, Am J Hum Genet 78, 38-51.
154.Martens, K., Heulens, I., Meulemans, S., Zaffanello, M., Tilstra, D., Hes, F. J., Rooman, R., Francois, I., de Zegher, F., Jaeken, J., Matthijs, G., and Creemers, J. W. (2007) Global distribution of the most prevalent deletions causing hypotonia-cystinuria syndrome, Eur J Hum Genet 15, 1029-1033.
155.Chabrol, B., Martens, K., Meulemans, S., Cano, A., Jaeken, J., Matthijs, G., and Creemers, J. W. (2008) Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome, J Med Genet 45, 314-318.
156.Martens, K., Jaeken, J., Matthijs, G., and Creemers, J. W. (2008) Multi-system disorder syndromes associated with cystinuria type I, Curr Mol Med 8, 544-550.
157.Parvari, R., and Hershkovitz, E. (2007) Chromosomal microdeletions and genes' functions: a cluster of chromosomal microdeletions and the deleted genes' functions, Eur J Hum Genet 15, 997-998.
158.Freude, K., Hoffmann, K., Jensen, L. R., Delatycki, M. B., des Portes, V., Moser, B., Hamel, B., van Bokhoven, H., Moraine, C., Fryns, J. P., Chelly, J., Gecz, J., Lenzner, S., Kalscheuer, V. M., and Ropers, H. H. (2004) Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation, Am J Hum Genet 75, 305-309.
159.Kleefstra, T., Brunner, H. G., Amiel, J., Oudakker, A. R., Nillesen, W. M., Magee, A., Genevieve, D., Cormier-Daire, V., van Esch, H., Fryns, J. P., Hamel, B. C., Sistermans, E. A., de Vries, B. B., and van Bokhoven, H. (2006) Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome, Am J Hum Genet 79, 370-377.
160.Kleefstra, T., Smidt, M., Banning, M. J., Oudakker, A. R., Van Esch, H., de Brouwer, A. P., Nillesen, W., Sistermans, E. A., Hamel, B. C., de Bruijn, D., Fryns, J. P., Yntema, H. G., Brunner, H. G., de Vries, B. B., and van Bokhoven, H. (2005) Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome, J Med Genet 42, 299-306.
161.Lawrence, J. G. (2002) Shared strategies in gene organization among prokaryotes and eukaryotes, Cell 110, 407-413.
162.Ferrier, D. E., and Holland, P. W. (2001) Ancient origin of the Hox gene cluster, Nat Rev Genet 2, 33-38.
163.Liebhaber, S. A. (1989) Alpha thalassemia, Hemoglobin 13, 685-731.
164.Higgs, D. R., Vickers, M. A., Wilkie, A. O., Pretorius, I. M., Jarman, A. P., and Weatherall, D. J. (1989) A review of the molecular genetics of the human alpha-globin gene cluster, Blood 73, 1081-1104.
165.Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., Antonarakis, S. E., Attwood, J., Baertsch, R., Bailey, J., Barlow, K., Beck, S., Berry, E., Birren, B., Bloom, T., Bork, P., Botcherby, M., Bray, N., Brent, M. R., Brown, D. G., Brown, S. D., Bult, C., Burton, J., Butler, J., Campbell, R. D., Carninci, P., Cawley, S., Chiaromonte, F., Chinwalla, A. T., Church, D. M., Clamp, M., Clee, C., Collins, F. S., Cook, L. L., Copley, R. R., Coulson, A., Couronne, O., Cuff, J., Curwen, V., Cutts, T., Daly, M., David, R., Davies, J., Delehaunty, K. D., Deri, J., Dermitzakis, E. T., Dewey, C., Dickens, N. J., Diekhans, M., Dodge, S., Dubchak, I., Dunn, D. M., Eddy, S. R., Elnitski, L., Emes, R. D., Eswara, P., Eyras, E., Felsenfeld, A., Fewell, G. A., Flicek, P., Foley, K., Frankel, W. N., Fulton, L. A., Fulton, R. S., Furey, T. S., Gage, D., Gibbs, R. A., Glusman, G., Gnerre, S., Goldman, N., Goodstadt, L., Grafham, D., Graves, T. A., Green, E. D., Gregory, S., Guigo, R., Guyer, M., Hardison, R. C., Haussler, D., Hayashizaki, Y., Hillier, L. W., Hinrichs, A., Hlavina, W., Holzer, T., Hsu, F., Hua, A., Hubbard, T., Hunt, A., Jackson, I., Jaffe, D. B., Johnson, L. S., Jones, M., Jones, T. A., Joy, A., Kamal, M., Karlsson, E. K., Karolchik, D., Kasprzyk, A., Kawai, J., Keibler, E., Kells, C., Kent, W. J., Kirby, A., Kolbe, D. L., Korf, I., Kucherlapati, R. S., Kulbokas, E. J., Kulp, D., Landers, T., Leger, J. P., Leonard, S., Letunic, I., Levine, R., Li, J., Li, M., Lloyd, C., Lucas, S., Ma, B., Maglott, D. R., Mardis, E. R., Matthews, L., Mauceli, E., Mayer, J. H., McCarthy, M., McCombie, W. R., McLaren, S., McLay, K., McPherson, J. D., Meldrim, J., Meredith, B., Mesirov, J. P., Miller, W., Miner, T. L., Mongin, E., Montgomery, K. T., Morgan, M., Mott, R., Mullikin, J. C., Muzny, D. M., Nash, W. E., Nelson, J. O., Nhan, M. N., Nicol, R., Ning, Z., Nusbaum, C., O'Connor, M. J., Okazaki, Y., Oliver, K., Overton-Larty, E., Pachter, L., Parra, G., Pepin, K. H., Peterson, J., Pevzner, P., Plumb, R., Pohl, C. S., Poliakov, A., Ponce, T. C., Ponting, C. P., Potter, S., Quail, M., Reymond, A., Roe, B. A., Roskin, K. M., Rubin, E. M., Rust, A. G., Santos, R., Sapojnikov, V., Schultz, B., Schultz, J., Schwartz, M. S., Schwartz, S., Scott, C., Seaman, S., Searle, S., Sharpe, T., Sheridan, A., Shownkeen, R., Sims, S., Singer, J. B., Slater, G., Smit, A., Smith, D. R., Spencer, B., Stabenau, A., Stange-Thomann, N., Sugnet, C., Suyama, M., Tesler, G., Thompson, J., Torrents, D., Trevaskis, E., Tromp, J., Ucla, C., Ureta-Vidal, A., Vinson, J. P., Von Niederhausern, A. C., Wade, C. M., Wall, M., Weber, R. J., Weiss, R. B., Wendl, M. C., West, A. P., Wetterstrand, K., Wheeler, R., Whelan, S., Wierzbowski, J., Willey, D., Williams, S., Wilson, R. K., Winter, E., Worley, K. C., Wyman, D., Yang, S., Yang, S. P., Zdobnov, E. M., Zody, M. C., and Lander, E. S. (2002) Initial sequencing and comparative analysis of the mouse genome, Nature 420, 520-562.
166.Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., Gocayne, J. D., Amanatides, P., Ballew, R. M., Huson, D. H., Wortman, J. R., Zhang, Q., Kodira, C. D., Zheng, X. H., Chen, L., Skupski, M., Subramanian, G., Thomas, P. D., Zhang, J., Gabor Miklos, G. L., Nelson, C., Broder, S., Clark, A. G., Nadeau, J., McKusick, V. A., Zinder, N., Levine, A. J., Roberts, R. J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy, S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K., Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A. E., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T. J., Higgins, M. E., Ji, R. R., Ke, Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G. V., Milshina, N., Moore, H. M., Naik, A. K., Narayan, V. A., Neelam, B., Nusskern, D., Rusch, D. B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C., Yao, A., Ye, J., Zhan, M., Zhang, W., Zhang, H., Zhao, Q., Zheng, L., Zhong, F., Zhong, W., Zhu, S., Zhao, S., Gilbert, D., Baumhueter, S., Spier, G., Carter, C., Cravchik, A., Woodage, T., Ali, F., An, H., Awe, A., Baldwin, D., Baden, H., Barnstead, M., Barrow, I., Beeson, K., Busam, D., Carver, A., Center, A., Cheng, M. L., Curry, L., Danaher, S., Davenport, L., Desilets, R., Dietz, S., Dodson, K., Doup, L., Ferriera, S., Garg, N., Gluecksmann, A., Hart, B., Haynes, J., Haynes, C., Heiner, C., Hladun, S., Hostin, D., Houck, J., Howland, T., Ibegwam, C., Johnson, J., Kalush, F., Kline, L., Koduru, S., Love, A., Mann, F., May, D., McCawley, S., McIntosh, T., McMullen, I., Moy, M., Moy, L., Murphy, B., Nelson, K., Pfannkoch, C., Pratts, E., Puri, V., Qureshi, H., Reardon, M., Rodriguez, R., Rogers, Y. H., Romblad, D., Ruhfel, B., Scott, R., Sitter, C., Smallwood, M., Stewart, E., Strong, R., Suh, E., Thomas, R., Tint, N. N., Tse, S., Vech, C., Wang, G., Wetter, J., Williams, S., Williams, M., Windsor, S., Winn-Deen, E., Wolfe, K., Zaveri, J., Zaveri, K., Abril, J. F., Guigo, R., Campbell, M. J., Sjolander, K. V., Karlak, B., Kejariwal, A., Mi, H., Lazareva, B., Hatton, T., Narechania, A., Diemer, K., Muruganujan, A., Guo, N., Sato, S., Bafna, V., Istrail, S., Lippert, R., Schwartz, R., Walenz, B., Yooseph, S., Allen, D., Basu, A., Baxendale, J., Blick, L., Caminha, M., Carnes-Stine, J., Caulk, P., Chiang, Y. H., Coyne, M., Dahlke, C., Mays, A., Dombroski, M., Donnelly, M., Ely, D., Esparham, S., Fosler, C., Gire, H., Glanowski, S., Glasser, K., Glodek, A., Gorokhov, M., Graham, K., Gropman, B., Harris, M., Heil, J., Henderson, S., Hoover, J., Jennings, D., Jordan, C., Jordan, J., Kasha, J., Kagan, L., Kraft, C., Levitsky, A., Lewis, M., Liu, X., Lopez, J., Ma, D., Majoros, W., McDaniel, J., Murphy, S., Newman, M., Nguyen, T., Nguyen, N., Nodell, M., Pan, S., Peck, J., Peterson, M., Rowe, W., Sanders, R., Scott, J., Simpson, M., Smith, T., Sprague, A., Stockwell, T., Turner, R., Venter, E., Wang, M., Wen, M., Wu, D., Wu, M., Xia, A., Zandieh, A., and Zhu, X. (2001) The sequence of the human genome, Science 291, 1304-1351.
167.Glazko, G. V., Koonin, E. V., Rogozin, I. B., and Shabalina, S. A. (2003) A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions, Trends Genet 19, 119-124.
168.Salgado, H., Moreno-Hagelsieb, G., Smith, T. F., and Collado-Vides, J. (2000) Operons in Escherichia coli: genomic analyses and predictions, Proc Natl Acad Sci U S A 97, 6652-6657.
169.Adachi, N., and Lieber, M. R. (2002) Bidirectional gene organization: a common architectural feature of the human genome, Cell 109, 807-809.
170.Byrd, P. J., Cooper, P. R., Stankovic, T., Kullar, H. S., Watts, G. D., Robinson, P. J., and Taylor, M. R. (1996) A gene transcribed from the bidirectional ATM promoter coding for a serine rich protein: amino acid sequence, structure and expression studies, Hum Mol Genet 5, 1785-1791.
171.Shintani, S., O'HUigin, C., Toyosawa, S., Michalova, V., and Klein, J. (1999) Origin of gene overlap: the case of TCP1 and ACAT2, Genetics 152, 743-754.
172.Normark, S., Bergstrom, S., Edlund, T., Grundstrom, T., Jaurin, B., Lindberg, F. P., and Olsson, O. (1983) Overlapping genes, Annu Rev Genet 17, 499-525.
173.Karlin, S., Chen, C., Gentles, A. J., and Cleary, M. (2002) Associations between human disease genes and overlapping gene groups and multiple amino acid runs, Proc Natl Acad Sci U S A 99, 17008-17013.
174.Fukuda, Y., Washio, T., and Tomita, M. (1999) Comparative study of overlapping genes in the genomes of Mycoplasma genitalium and Mycoplasma pneumoniae, Nucleic Acids Res 27, 1847-1853.
175.Myers, G. (1999) A dataset generator for whole genome shotgun sequencing, Proc Int Conf Intell Syst Mol Biol, 202-210.
176.Bentley, D. R. (2000) The Human Genome Project--an overview, Med Res Rev 20, 189-196.
177.Ott, B. B. (1995) The Human Genome Project: an overview of ethical issues and public policy concerns, Nurs Outlook 43, 228-231.
178.Uzych, L. (1996) The Human Genome project: an overview of ethical issues and public policy concerns, Nurs Outlook 44, 150-151.
179.Li, Y. Y., Yu, H., Guo, Z. M., Guo, T. Q., Tu, K., and Li, Y. X. (2006) Systematic analysis of head-to-head gene organization: evolutionary conservation and potential biological relevance, PLoS Comput Biol 2, e74.
180.Moreno-Hagelsieb, G., Trevino, V., Perez-Rueda, E., Smith, T. F., and Collado-Vides, J. (2001) Transcription unit conservation in the three domains of life: a perspective from Escherichia coli, Trends Genet 17, 175-177.
181.Moreno-Hagelsieb, G., and Collado-Vides, J. (2002) Operon conservation from the point of view of Escherichia coli, and inference of functional interdependence of gene products from genome context, In Silico Biol 2, 87-95.
182.Zhang, X., and Smith, T. F. (1998) Yeast "operons", Microb Comp Genomics 3, 133-140.
183.Coggan, M., Whitbread, L., Whittington, A., and Board, P. (1998) Structure and organization of the human theta-class glutathione S-transferase and D-dopachrome tautomerase gene complex, Biochem J 334 ( Pt 3), 617-623.
184.Gaston, K., and Fried, M. (1994) YY1 is involved in the regulation of the bi-directional promoter of the Surf-1 and Surf-2 genes, FEBS Lett 347, 289-294.
185.Zanotto, E., Shah, Z. H., and Jacobs, H. T. (2007) The bidirectional promoter of two genes for the mitochondrial translational apparatus in mouse is regulated by an array of CCAAT boxes interacting with the transcription factor NF-Y, Nucleic Acids Res 35, 664-677.
186.Pandey, R. R., Ceribelli, M., Singh, P. B., Ericsson, J., Mantovani, R., and Kanduri, C. (2004) NF-Y regulates the antisense promoter, bidirectional silencing, and differential epigenetic marks of the Kcnq1 imprinting control region, J Biol Chem 279, 52685-52693.
187.Blanchard, Y., Seenundun, S., and Robaire, B. (2007) The promoter of the rat 5α-reductase type 1 gene is bidirectional and Sp1-dependent, Mol Cell Endocrinol 264, 171-183.
188.Zhu, Q. S., Chen, K., and Shih, J. C. (1994) Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1, J Neurosci 14, 7393-7403.
189.DeClerck, Y. A., Mercurio, A. M., Stack, M. S., Chapman, H. A., Zutter, M. M., Muschel, R. J., Raz, A., Matrisian, L. M., Sloane, B. F., Noel, A., Hendrix, M. J., Coussens, L., and Padarathsingh, M. (2004) Proteases, extracellular matrix, and cancer: a workshop of the path B study section, Am J Pathol 164, 1131-1139.
190.Bol, S., Belge, G., Thode, B., Bartnitzke, S., and Bullerdiek, J. (1999) Structural abnormalities of chromosome 2 in benign thyroid tumors. Three new cases and review of the literature, Cancer Genet Cytogenet 114, 75-77.
191.Ueda, T., Komiya, A., Suzuki, H., Shimbo, M., Sakamoto, S., Imamoto, T., Akakura, K., Shiraishi, T., and Ichikawa, T. (2005) Loss of heterozygosity on chromosome 2 in Japanese patients with prostate cancer, Prostate 64, 265-271.
192.Matyakhina, L., Pack, S., Kirschner, L. S., Pak, E., Mannan, P., Jaikumar, J., Taymans, S. E., Sandrini, F., Carney, J. A., and Stratakis, C. A. (2003) Chromosome 2 (2p16) abnormalities in Carney complex tumours, J Med Genet 40, 268-277.
193.Brooks, A. S., Breuning, M. H., Osinga, J., vd Smagt, J. J., Catsman, C. E., Buys, C. H., Meijers, C., and Hofstra, R. M. (1999) A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome), J Med Genet 36, 485-489.
194.Halal, F., and Morel, J. (1990) The syndrome of Hirschsprung disease, microcephaly, unusual face, and mental retardation, Am J Med Genet 37, 106-108.
195.Mowat, D. R., Croaker, G. D., Cass, D. T., Kerr, B. A., Chaitow, J., Ades, L. C., Chia, N. L., and Wilson, M. J. (1998) Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23, J Med Genet 35, 617-623.
196.Lin, J. M., Collins, P. J., Trinklein, N. D., Fu, Y., Xi, H., Myers, R. M., and Weng, Z. (2007) Transcription factor binding and modified histones in human bidirectional promoters, Genome Res 17, 818-827.
197.Skrabanek, L., and Wolfe, K. H. (1998) Eukaryote genome duplication - where's the evidence?, Curr Opin Genet Dev 8, 694-700.
198.Koyanagi, K. O., Hagiwara, M., Itoh, T., Gojobori, T., and Imanishi, T. (2005) Comparative genomics of bidirectional gene pairs and its implications for the evolution of a transcriptional regulation system, Gene 353, 169-176.
199.Kawai, Y., Asai, K., Miura, Y., Inoue, Y., Yamamoto, M., Moriyama, A., Yamamoto, N., and Kato, T. (2003) Structure and promoter activity of the human glia maturation factor-gamma gene: a TATA-less, GC-rich and bidirectional promoter, Biochim Biophys Acta 1625, 246-252.
200.Ito, E., Xie, G., Maruyama, K., and Palmer, P. P. (2000) A core-promoter region functions bi-directionally for human opioid-receptor-like gene ORL1 and its 5'-adjacent gene GAIP, J Mol Biol 304, 259-270.
201.Zhang, L. F., Ding, J. H., Yang, B. Z., He, G. C., and Roe, C. (2003) Characterization of the bidirectional promoter region between the human genes encoding VLCAD and PSD-95, Genomics 82, 660-668.
202.Linton, J. P., Yen, J. Y., Selby, E., Chen, Z., Chinsky, J. M., Liu, K., Kellems, R. E., and Crouse, G. F. (1989) Dual bidirectional promoters at the mouse dhfr locus: cloning and characterization of two mRNA classes of the divergently transcribed Rep-1 gene, Mol Cell Biol 9, 3058-3072.
203.Emoto, M., Miki, M., Sarker, A. H., Nakamura, T., Seki, Y., Seki, S., and Ikeda, S. (2005) Structure and transcription promoter activity of mouse flap endonuclease 1 gene: alternative splicing and bidirectional promoter, Gene 357, 47-54.
204.Engstrom, P. G., Suzuki, H., Ninomiya, N., Akalin, A., Sessa, L., Lavorgna, G., Brozzi, A., Luzi, L., Tan, S. L., Yang, L., Kunarso, G., Ng, E. L., Batalov, S., Wahlestedt, C., Kai, C., Kawai, J., Carninci, P., Hayashizaki, Y., Wells, C., Bajic, V. B., Orlando, V., Reid, J. F., Lenhard, B., and Lipovich, L. (2006) Complex Loci in human and mouse genomes, PLoS Genet 2, e47.
205.Chen, P. Y., Chang, W. S., Chou, R. H., Lai, Y. K., Lin, S. C., Chi, C. Y., and Wu, C. W. (2007) Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner, BMC Mol Biol 8, 2.
206.Hayashi, R., Ueda, T., Farwell, M. A., and Takeuchi, N. (2007) Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene, Mitochondrion 7, 195-203.
207.van Waveren, C., and Moraes, C. T. (2008) Transcriptional co-expression and co-regulation of genes coding for components of the oxidative phosphorylation system, BMC Genomics 9, 18.
208.Lenka, N., Vijayasarathy, C., Mullick, J., and Avadhani, N. G. (1998) Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex, Prog Nucleic Acid Res Mol Biol 61, 309-344.
209.Ongwijitwat, S., and Wong-Riley, M. T. (2005) Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons?, Gene 360, 65-77.
210.Villena, J. A., Vinas, O., Mampel, T., Iglesias, R., Giralt, M., and Villarroya, F. (1998) Regulation of mitochondrial biogenesis in brown adipose tissue: nuclear respiratory factor-2/GA-binding protein is responsible for the transcriptional regulation of the gene for the mitochondrial ATP synthase beta subunit, Biochem J 331 ( Pt 1), 121-127.
211.Collins, P. J., Kobayashi, Y., Nguyen, L., Trinklein, N. D., and Myers, R. M. (2007) The ets-related transcription factor GABP directs bidirectional transcription, PLoS Genet 3, e208.
212.Huang, C. C., and Chang, W. S. (2009) Cooperation between NRF-2 and YY-1 transcription factors is essential for triggering the expression of the PREPL-C2ORF34 bidirectional gene pair, BMC Mol Biol 10, 67.
213.Komuro, I., and Izumo, S. (1993) Csx: a murine homeobox-containing gene specifically expressed in the developing heart, Proc Natl Acad Sci U S A 90, 8145-8149.
214.Lints, T. J., Parsons, L. M., Hartley, L., Lyons, I., and Harvey, R. P. (1993) Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants, Development 119, 969.
215.Bodmer, R., and Venkatesh, T. V. (1998) Heart development in Drosophila and vertebrates: conservation of molecular mechanisms, Dev Genet 22, 181-186.
216.Lyons, I., Parsons, L. M., Hartley, L., Li, R., Andrews, J. E., Robb, L., and Harvey, R. P. (1995) Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5, Genes Dev 9, 1654-1666.
217.Chen, C. Y., and Schwartz, R. J. (1995) Identification of novel DNA binding targets and regulatory domains of a murine tinman homeodomain factor, nkx-2.5, J Biol Chem 270, 15628-15633.
218.Treisman, R. (1986) Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors, Cell 46, 567-574.
219.Chen, C. Y., and Schwartz, R. J. (1997) Competition between negative acting YY1 versus positive acting serum response factor and tinman homologue Nkx-2.5 regulates cardiac alpha-actin promoter activity, Mol Endocrinol 11, 812-822.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top