摘要
第八型脊髓小腦共濟失調症(SCA8)是第一個被報導的單一三核苷重複擴增突變、由DNA兩股分別產生致病性的RNA (ATXN8OS)及蛋白質(ATXN8)產物的疾病。SCA8外顯性不完全，基因突變也見於極少數正常人及其他神經性疾病。ATXN8OS基因5’端有明顯的CpG島。本研究首先檢視正常人族群及帕金森氏症患者、原發性顫抖症及其他神經相關疾病患者族群之SCA8基因CTG重複變異，結果共發現一位正常人及兩位相關的肌肉營養不良症患者具CTG重複擴增的對偶基因。其次，在SCA8外遺傳研究方面，利用SCA8 CTG擴增的病人及其家屬及帶有SCA8 0~157個複合重複序列的胚胎腎細胞株DNA樣品，以PCR-based限制酵素及bisulfite定序技術，檢測ATXN8OS與KLHL1基因重疊序列上的CpG島甲基化情形。結果並未觀察到甲基化現象。另外也利用辨識緊密或疏鬆染色質結構的抗體及染色質免疫沈澱-PCR技術，來檢測SCA8基因的染色質結構。結果觀察到與CTG重複擴增相關的緊密染色質結構，但與DNA甲基化無關。最後，利用年齡、性別配對的正常人和CTG重複擴增病患的淋巴細胞株，探討對細胞自戕刺激物staurosporine或proteasome抑制劑MG-132的敏感性。病人淋巴細胞株在staurosporine (50 nM)及MG-132 (200 nM)濃度處理下，細胞死亡率顯著增加的結果，顯示SCA8的CTG重複擴增具細胞毒性。

Abstract
Spinocerebellar ataxia type 8 (SCA8) involves the expression of an expanded CTG/CAG combined repeats from opposite strands producing CUG expansion transcripts (ATXN8OS) and a polyglutamine expansion protein (ATXN8). SCA8 disease does not show complete penetrance and repeat expansions have been found among unaffected individuals and patients with other neurological diseases. An apparent CpG island was observed within the 5’ region of the ATXN8OS gene. In this study, we screened the SCA8 CTG repeats distribution in normal controls and in patients with various neurodegenerative diseases. A tatal of three subjects with expanded alleles was found, including one normal and two related oculopharyngeal muscular dystrophy. In the epigenetic studies, aberrant methylation in the overlapped ATXN8OS/KLHL1 gene exon 1 region was evaluated using DNA samples from patients with SCA8 expansions and stable HEK-293 lines carrying 0~157 combined repeats. PCR-based restriction enzyme assay and bisulfite-sequencing assay were performed for the measurement of CpG hypermethylation. No methylation was observed. Additionally, chromatin immunoprecipitation and PCR using antibody associated with repressed or open chromatin were performed to examine the chromatin structure of the SCA8 gene. A repeat length-dependent repression of chromatin structure, which is independent of DNA methylation, was observed. Finally, age and gender-matched lymphoblastoid cells with or without expanded SCA8 alleles were tested for their sensitivity to staurosporine (apoptotic stimulus) and MG-132 (proteosome inhibitor). The results of significant increase of cell death by staurosporine (50 nM) and MG-132 (200 nM) treatment further demonstrate that the expanded SCA8 repeats are toxic to human cells.

目錄 I
中文摘要 IV
英文摘要 V
圖表次 VI
壹、緒論 1
一、脊髓小腦共濟失調症(SCA) 1
二、第八型脊髓小腦共濟失調症(SCA8) 3
三、SCA8的可能致病機轉 4
(一) KLHL1的功能缺失(loss of function) 5
(二) RNA gain-of function 5
(三) PolyQ擴增蛋白 6
四、外遺傳(Epigenetic)修飾與基因表現的調節 7
(一) DNA甲基化 7
(二) 組蛋白修飾 8
(三) 三核苷酸重複擴增和染色質結構 8
五、SCA的淋巴細胞株模式研究 9
六、研究動機與目的 10
貳、研究材料與方法 12
一、研究材料 12
二、細胞株的培養及冷凍保存 12
三、基因組DNA萃取 13
四、SCA8 (CTG)n重複分析 14
五、PCR-based限制酶檢測 14
六、Sodium-bisulfat定序 15
七、染色質免疫沈澱-PCR (ChIP- PCR) 16
八、淋巴細胞的存活率分析 18
九、caspase-3活性分析 19
參、結果 20
一、SCA8 CTA/CTG重複之遺傳分析 20
二、SCA8外遺傳研究(epigenetic studies) 20
(一) H327、H600家族的DNA甲基化分析 20
(二) SCA8胚胎腎臟細胞株的DNA甲基化分析 22
(三) SCA8胚胎腎臟細胞株的染色質結構分析 23
(四) SCA8淋巴細胞株的染色質結構分析 23
三、 SCA8淋巴細胞株的細胞存活率分析 24
四、 SCA8淋巴細胞株的caspase-3活性分析 25
肆、討論 26
一、 SCA8 CTA/CTG重複之遺傳分析 26
二、 SCA8外遺傳研究 27
(一) DNA甲基化分析 27
(二) 染色質結構分析 28
(三) DNA甲基化與組蛋白修飾之關係 30
三、 SCA8淋巴細胞株的細胞存活率與caspase-3活性分析 31
伍、參考文獻 34
陸、附錄圖表 46

洪葦苓 (2005)。第八型脊髓小腦運動失調症：CTG三核苷重複的遺傳分析與細胞模式研究。國立臺灣師範大學生命科學系碩士論文。
黃淑宜 (2006)。人類遺傳疾病：第一部份-第八型脊髓小腦共濟失調症之分子遺傳及外遺傳研究；第二部份-台灣兩個Netherton徵候群病患家族之分子遺傳研究。國立台灣師範大學生命科學系碩士論文。
林玄原 (2007)。脊髓小腦運動失調症之族群遺傳分析與CTG三核苷重複擴增的分子致病研究。國立台灣師範大學生命科學系博士論文。
Al-Mahdawi, S., Pinto, R. M., Ismail, O., Varshney, D., Lymperi, S., Sandi, C., Trabzuni, D., and Pook, M. (2008). The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum Mol Genet 17, 735-746.
Aromolaran, K. A., Benzow, K. A., Koob, M. D., and Piedras-Renteria, E. S. (2007). The Kelch-like protein 1 modulates P/Q-type calcium current density. Neuroscience 145, 841-850.
Bannister, A. J., Zegerman, P., Partridge, J. F., Miska, E. A., Thomas, J. O., Allshire, R. C., and Kouzarides, T. (2001). Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120-124.
Bannister, A. J., Schneider, R., and Kouzarides, T. (2002). Histone methylation: dynamic or static? Cell 109, 801-806.
Benzow, K. A., and Koob, M. D. (2002). The KLHL1-antisense transcript (KLHL1AS) is evolutionarily conserved. Mamm Genome 13, 134-141.
Bernstein, B. E., Meissner, A., and Lander, E. S. (2007). The mammalian epigenome. Cell 128, 669-681.
Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev 16, 6-21.
Borovecki, F., Lovrecic, L., Zhou, J., Jeong, H., Then, F., Rosas, H. D., Hersch, S. M., Hogarth, P., Bouzou, B., Jensen, R. V., and Krainc, D. (2005). Genome-wide expression profiling of human blood reveals biomarkers for Huntington’s disease. Proc Natl Acad Sci USA 102, 11023-11028.
Bowman, A. B., Yoo, S. Y., Dantuma, N. P., and Zoghbi, H. Y. (2005). Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum Mol Genet 14, 679-691.
Brook, J. D., McCurrach, M. E., Harley, H. G., Buckler, A. J., Church, D., Aburatani, H., Hunter, K., Stanton, V. P., Thirion, J. P., Hudson, T., and et al. (1992). Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell 68, 799-808.
Cagnoli, C., Mariotti, C., Taroni, F., Seri, M., Brussino, A., Michielotto, C., Grisoli, M., Di Bella, D., Migone, N., Gellera, C., et al. (2006). SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain 129, 235-242.
Charlet-B, N., Savkur, R. S., Singh, G., Philips, A. V., Grice, E. A., and Cooper, T. A. (2002). Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 10, 45-53.
Chen, D. H., Brkanac, Z., Verlinde, C. L., Tan, X. J., Bylenok, L., Nochlin, D., Matsushita, M., Lipe, H., Wolff, J., Fernandez, M., Cimino, P. J., Bird, T. D., and Raskind, W. H. (2003). Missense mutations in the regulatory domain of PKCγ: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet 72, 839-849.
Ciechanover, A. (1994). The ubiquitin-proteasome proteolytic pathway. Cell 79, 13-21.
Colin, E., Régulier, E., Perrin, V., Dürr, A., Brice, A., Aebischer, P., Déglon, N., Humbert, S., and Saudou, F. (2005). Akt is altered in an animal model of Huntington's disease and in patients. Eur J Neurosci 21, 1478-88.
Day, J. W., Schut, L. J., Moseley, M. L., Durand, A. C., and Ranum, L. P. (2000). Spinocerebellar ataxia type 8: clinical features in a large family. Neurology 55, 649-657.
Dion, V., Lin, Y., Price, B. A., Fyffe, S. L., Seluanov, A., Gorbunova, V., and Wilson, J. H. (2008). Genome-wide demethylation promotes triplet repeat instability independently of homologous recombination. DNA Repair (Amst) 7, 313-320.
Fardaei, M., Rogers, M. T., Thorpe, H. M., Larkin, K., Hamshere, M. G., Harper, P. S., and Brook, J. D. (2002). Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells. Hum Mol Genet 11, 805-814.
Fischle, W., Wang, Y., Jacobs, S. A., Kim, Y., Allis, C. D., and Khorasanizadeh, S. (2003). Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 17, 1870-1881.
Fu, Y. H., Pizzuti, A., Fenwick, R. G., Jr., King, J., Rajnarayan, S., Dunne, P. W., Dubel, J., Nasser, G. A., Ashizawa, T., de Jong, P., and et al. (1992). An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255, 1256-1258.
Fuentes-Prior, P., and Salvesen, G. S. (2004). The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J 384, 201-232.
Fuks, F., Hurd, P. J., Wolf, D., Nan, X., Bird, A. P., and Kouzarides, T. (2003). The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278, 4035-4040.
Glickman, M. H., and Ciechanover, A. (2002). The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82, 373-428.
Gorbunova, V., Seluanov, A., Mittelman, D., and Wilson, J. H. (2004). Genome-wide demethylation destabilizes CTG.CAG trinucleotide repeats in mammalian cells. Hum Mol Genet 13, 2979-2989.
Greene, E., Mahishi, L., Entezam, A., Kumari, D., and Usdin, K. (2007). Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res 35, 3383-3390.
Grewal, R. P., Tayag, E., Figueroa, K. P., Zu, L., Durazo, A., Nunez, C., and Pulst, S. M. (1998). Clinical and genetic analysis of a distinct autosomal dominant spinocerebellar ataxia. Neurology 51, 1423-1426.
Handa, V., Goldwater, D., Stiles, D., Cam, M., Poy, G., Kumari, D., and Usdin, K. (2005). Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles. FEBS Lett 579, 2702-2708.
He, Y., Zu, T., Benzow, K. A., Orr, H. T., Clark, H. B., and Koob, M. D. (2006). Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J Neurosci 26, 9975-9982.
Holmes, S. E., O'Hearn, E. E., McInnis, M. G., Gorelick-Feldman, D. A., Kleiderlein, J. J., Callahan, C., Kwak, N. G., Ingersoll-Ashworth, R. G., Sherr, M., Sumner, A. J., Sharp, A. H., Ananth, U., Seltzer, W. K., Boss, M. A., Vieria-Saecker, A. M., Epplen, J. T., Riess, O., Ross, C. A., and Margolis, R. L. (1999). Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nat Genet 23, 391-392.
Ikeda, Y., Shizuka, M., Watanabe, M., Okamoto, K., and Shoji, M. (2000). Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan. Neurology 54, 950-955.
Ikeda, Y., Dalton, J. C., Moseley, M. L., Gardner, K. L., Bird, T. D., Ashizawa, T., Seltzer, W. K., Pandolfo, M., Milunsky, A., Potter, N. T., Shoji, M., Vincent, J. B., Day, J. W., and Ranum, L. P. (2004). Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia. Am J Hum Genet 75, 3-16.
Ikeda, Y., Dick, K. A., Weatherspoon, M. R., Gincel, D., Armbrust, K. R., Dalton, J. C., Stevanin, G., Durr, A., Zuhlke, C., Burk, K., et al. (2006). Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet 38, 184-190.
Ikeda, Y., Daughters, R. S., and Ranum, L. P. (2007). Bidirectional expression of the SCA8 expansion mutation: One mutation, two genes. Cerebellum, 1-9.
Jones, P. L., Veenstra, G. J., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., and Wolffe, A. P. (1998). Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19, 187-191.
Juvonen, V., Kairisto, V., Hietala, M., and Savontaus, M. L. (2002). Calculating predictive values for the large repeat alleles at the SCA8 locus in patients with ataxia. J Med Genet 39, 935-936.
Koeppen, A. H. (2005). The pathogenesis of spinocerebellar ataxia. Cerebellum 4, 62-73.
Koob, M. D., Moseley, M. L., Schut, L. J., Benzow, K. A., Bird, T. D., Day, J. W., and Ranum, L. P. (1999). An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 21, 379-384.
Kouzarides, T. (2002). Histone methylation in transcriptional control. Curr Opin Genet Dev 12, 198-209.
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116-120.
Mahadevan, M., Tsilfidis, C., Sabourin, L., Shutler, G., Amemiya, C., Jansen, G., Neville, C., Narang, M., Barcelo, J., O'Hoy, K., and et al. (1992). Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science 255, 1253-1255.
Manto, M. U. (2005). The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 4, 2-6.
McCampbell, A., Taylor, J. P., Taye, A. A., Robitschek, J., Li, M., Walcott, J., Merry, D., Chai, Y., Paulson, H., Sobue, G., and Fischbeck, K. H. (2000). CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 9, 2197-2202.
Michalik, A., and Van Broeckhoven, C. (2003). Pathogenesis of polyglutamine disorders: aggregation revisited. Hum Mol Genet 12 Spec No 2, R173-186.
Miller, J. W., Urbinati, C. R., Teng-Umnuay, P., Stenberg, M. G., Byrne, B. J., Thornton, C. A., and Swanson, M. S. (2000). Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. Embo J 19, 4439-4448.
Moseley, M. L., Zu, T., Ikeda, Y., Gao, W., Mosemiller, A. K., Daughters, R. S., Chen, G., Weatherspoon, M. R., Clark, H. B., Ebner, T. J., et al. (2006). Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 38, 758-769.
Mosemiller, A. K., Dalton, J. C., Day, J. W., and Ranum, L. P. W. (2003). Molecular genetics of spinocerebellar ataxia type 8 (SCA8). Cytogenet Genome Res 100; 175-183.
Mutsuddi, M., Marshall, C. M., Benzow, K. A., Koob, M. D., and Rebay, I. (2004). The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Curr Biol 14, 302-308.
Mutsuddi, M., and Rebay, I. (2005). Molecular genetics of spinocerebellar ataxia type 8 (SCA8). RNA Biol 2, 49-52.
Myung, J., Kim, K. B., and Crews, C. M. (2001). The ubiquitin-proteasome pathway and proteasome inhibitors. Med Res Rev 21, 245-273.
Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., and Bird, A. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386-389.
Nemes, J. P., Benzow, K. A., Moseley, M. L., Ranum, L. P., and Koob, M. D. (2000). The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a novel actin-binding protein (KLHL1). Hum Mol Genet 9, 1543-1551.
Ng, H. H., Robert, F., Young, R. A., and Struhl, K. (2003). Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 11, 709-719.
Nishioka, K., Chuikov, S., Sarma, K., Erdjument-Bromage, H., Allis, C. D., Tempst, P., and Reinberg, D. (2002). Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16, 479-489.
Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D. M., and Nakatani, Y. (2002). A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296, 1132-1136.
Otten, A. D., and Tapscott, S. J. (1995). Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci USA 92, 5465-5469.
Perez, M. K., Paulson, H. L., Pendse, S. J., Saionz, S. J., Bonini, N. M., and Pittman, R. N. (1998). Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol 143, 1457-1470.
Pietrobono, R., Tabolacci, E., Zalfa, F., Zito, I., Terracciano, A., Moscato, U., Bagni, C., Oostra, B., Chiurazzi, P., and Neri, G. (2005). Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 14, 267-277.
Ranum, L. P., and Day, J. W. (2004). Pathogenic RNA repeats: an expanding role in genetic disease. Trends Genet 20, 506-512.
Robinson, D. N., and Cooley, L. (1997). Drosophila kelch is an oligomeric ring canal actin organizer. J Cell Biol 138, 799-810.
Savkur, R. S., Philips, A. V., and Cooper, T. A. (2001). Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 29, 40-47.
Schols, L., Szymanski, S., Peters, S., Przuntek, H., Epplen, J. T., Hardt, C., and Riess, O. (2000). Genetic background of apparently idiopathic sporadic cerebellar ataxia. Hum Genet 107, 132-137.
Schols, L., Bauer, I., Zühlke, C., Schulte, T., Kölmel, C., Bürk, K., Topka, H., Bauer, P., Przuntek, H., and Riess, O. (2003). Do CTG expansions at the SCA8 locus cause ataxia? Ann Neurol 54, 110-115.
Schols, L., Bauer, P., Schmidt, T., Schulte, T., and Riess, O. (2004). Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3, 291-304.
Sedkov, Y., Cho, E., Petruk, S., Cherbas, L., Smith, S. T., Jones, R. S., Cherbas, P., Canaani, E., Jaynes, J. B., and Mazo, A. (2003). Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila. Nature 426, 78-83.
Seng, S., Avraham, H. K., Jiang, S., Venkatesh, S., and Avraham, S. (2006). KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol 26, 8371-8384.
Silveira, I., Alonso, I., Guimaraes, L., Mendonca, P., Santos, C., Maciel, P., Fidalgo De Matos, J. M., Costa, M., Barbot, C., Tuna, A., et al. (2000). High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles. Am J Hum Genet 66, 830-840.
Sobrido, M. J., Cholfin, J. A., Perlman, S., Pulst, S. M., Geschwind, D. H. (2001). SCA8 repeat expansions in ataxia: a controversial association. Neurology 57, 1310-1312.
Soong, B. W., Lu, Y. C., Choo, K. B., and Lee, H. Y. (2001). Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6. Arch Neurol 58, 1105-1109.
Stevanin, G., Herman, A., Durr, A., Jodice, C., Frontali, M., Agid, Y., and Brice, A. (2000). Are (CTG)n expansions at the SCA8 locus rare polymorphisms? Nat Genet 24, 213; author reply 215.
Strahl, B. D., and Allis, C. D. (2000). The language of covalent histone modifications. Nature 403, 41-45.
Tachibana, M., Sugimoto, K., Fukushima, T., and Shinkai, Y. (2001). Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276, 25309-25317.
Tsai, H. F., Lin, S. J., Li, C., and Hsieh, M. (2005). Decreased expression of Hsp27 and Hsp70 in transformed lymphoblastoid cells from patients with spinocerebellar ataxia type 7. Biochem Biophys Res Commun 334, 1279-1286.
Tufarelli, C., Stanley, J. A., Garrick, D., Sharpe, J. A., Ayyub, H., Wood, W. G., and Higgs, D. R. (2003). Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat Genet 34, 157-165.
van Swieten, J. C., Brusse, E., de Graaf, B. M., Krieger, E., van de Graaf, R., de Koning, I., Maat-Kievit, A., Leegwater, P., Dooijes, D., Oostra, B. A., and Heutink, P. (2003). A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet 72, 191-199.
Worth, P. F., Houlden, H., Giunti, P., Davis, M. B., and Wood, N. W. (2000). Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia. Nat Genet 24, 214-215.
Wu, Y. R., Lin, H. Y., Chen, C. M., Gwinn-Hardy, K., Ro, L. S., Wang, Y. C., Li, S. H., Hwang, J. C., Fang, K., Hsieh-Li, H. M., Li, M. L., Tung, L. C., Su, M. T., Lu, K. T., Lee-Chen, G. J. (2004). Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson’s disease. Clin Genet 65, 209-214.
Yamada, M., Sato, T., Shimohata, T., Hayashi, S., Igarashi, S., Tsuji, S., and Takahashi, H. (2001). Interaction between neuronal intranuclear inclusions and promyelocytic leukemia protein nuclear and coiled bodies in CAG repeat diseases. Am J Pathol 159, 1785-1795.
Yan, C., and Boyd, D. D. (2006). Histone H3 acetylation and H3 K4 methylation define distinct chromatin regions permissive for transgene expression. Mol Cell Biol 26, 357-6371.
Yang, L., Xia, L., Wu, D. Y., Wang, H., Chansky, H. A., Schubach, W. H., Hickstein, D. D., and Zhang, Y. (2002). Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene 21, 148-152.
Yu, G. Y., Howell, M. J., Roller, M. J., Xie, T. D., and Gomez, C. M. (2005). Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol 57, 349-354.
Zegerman, P., Canas, B., Pappin, D., and Kouzarides, T. (2002). Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J Biol Chem 277, 11621-11624.