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研究生:陳美齡
研究生(外文):Mei-Ling Chen
論文名稱:T細胞接受器α/δ基因座內高保留度DNA片段與調控此接受器基因表現的細胞核蛋白質因子間交互作用之研究
論文名稱(外文):Studies of Functional Interactions between a Highly Conserved DNA Element Located in the T Cell Receptor (TCR) α/δ Locus and the Nuclear Factors Involved in the Regulation of TCR Gene Expression
指導教授:果伽蘭
指導教授(外文):Chia -Lam Kuo
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
中文關鍵詞:T 細胞接受器高保留度 DNA 片段
外文關鍵詞:Conserved Sequence BlockT cell receptor
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中文摘要
CSB (Conserved Sequence Block) 為座落於 T 細胞接受器 α/δ 基因座內 Jα 基因片段 Jα3 和 Jα4 之間的一段包含 125 個核■酸的 DNA 片段。 其序列在人和老鼠之間呈現高度保留的特性 (95% similarity)﹐此保留的程度遠比T細胞接受器 α/δ 基因座內其他已知的調節元素在人和老鼠間之相似性來的高。 早期研究發現﹐當以 CSB 作為探針和老鼠不同組織的訊息RNA (mRNA) 進行雜合反應 (hybridization) 時﹐ 並無法偵測到雜合訊號﹐此一結果顯示 CSB 並不會被轉錄為RNA。此外﹐以 CSB 為探針進行 genomic zoo blot 分析時發現﹐很多脊椎動物的基因體 DNA (genomic DNA) 都出現雜合訊號﹐此結果意味著 CSB 序列在其他脊椎動物似乎亦是被保留的。 從上述 CSB 的特色可以推論﹐CSB 很可能具有調控 T 細胞接受器 α/δ 基因座內基因的重組或表現之功能。
在本論文的研究中﹐即以各種生化及分子生物學的方法來探究 CSB 可能的功能。 由 transient transfection 的結果顯示﹐當 CSB 和 T細胞接受器 α 加強子共同接於 CAT 基因的表現載體時﹐可使 T 細胞接受器 α 加強子的活性增加兩倍﹐而 CSB 本身則不具有促進基因表現的活性。 EMSA (Electrophoretic Mobility Shift Assay) 的結果顯示淋巴特異性及 T 細胞特異性的細胞核因子﹐均參與 CSB 結合複合體的生成﹐且 CSB-蛋白質複合體的生成隱含了極為錯綜複雜的 "CSB 與蛋白質之間" 及 "蛋白質與蛋白質之間" 的交互作用。這些結果顯示 CSB 是一個可和多個組織特異性的細胞核因子結合﹐且能促使 T 細胞接受器 α 加強子活性增強的調節性元素。
T 細胞接受器基因的重組及表現是具發育時期特異性的 (developmental stage specific)。在本論文的第二部份即研究 CSB 結合因子於 T 細胞的不同發育時期及老鼠各種不同發育時期的器官之表現情形﹐以進一步瞭解 CSB 的功能。實驗結果顯示﹐某些參與 CSB 結合複合體生成的細胞核因子之表現是具發育時期特異性的。 同時﹐本部份的實驗結果亦證明 Oct-1 及具淋巴特異性的 GATA-3﹑Oct-2 等 DNA 結合蛋白﹐在老鼠胸腺細胞中均參與 in vitro 及 in vivo CSB 結合複合體的生成。 另外﹐本論文的研究結果亦發現﹐小雞器官的細胞核萃取液和老鼠相似﹐都具有形成組織特異性 CSB 結合複合體的能力﹐且 GATA-3 及 Oct-2 等在演化過程中被保留的 DNA 結合蛋白﹐亦參與小雞 in vitro CSB 結合複合體的生成。
綜合本論文所得的結果可以推論﹐CSB 的功能很可能是藉由調控 T 細胞接受器 α/δ 基因座中與 CSB 相鄰的 Jα 區域之染色質結構﹐使得該區域中 V到 Jα 的重組在 T細胞發育過程中得以在適當的空間及時間下進行。進一步鑑定與 CSB 交互作用的蛋白質因子﹐將有助於瞭解調控 T 細胞接受器 α/δ 基因座在 T 細胞發育過程中﹐基因重組和表現的分子機制。
Abstract
CSB (Conserved Sequence Block), a block of 125 nucleotide in length, is located between Jα3 and Jα4, approximately 5 kb to the 5'' end of Cα exon l, and its sequence is highly conserved between human and mouse. There are only six differences over 125 nucleotide positions (95% similar). This degree of conservation is much higher than the ~71% overall sequence similarity found between human and mouse in the non-coding region of the TCR Cα/Cδ loci, and is also higher than that obtained when TCR α enhancer region sequences are compared. In addition, no transcript was shown to hybridize to the CSB region in different mouse tissues and zoo blot analysis using the CSB as a probe suggests that this sequence may be conserved in other vertebrates. Given these observations, it seems plausible that this conserved sequence may play a role relevant to the evolutionarily conserved coordinate regulation of TCR gene expression/rearrangement.
In this study, a series of detailed analyses were performed to explore the function of CSB. Transient transfection results showed that the CSB-containing element in conjunction with the TCR α enhancer up-regulated the α enhancer activity, whereas no enhancer activity was detected when CSB alone was assayed. In vitro occupancy analyses of CSB by nuclear factors revealed the existence of an unexpectedly intricate network of CSB-protein and protein-protein interactions. Lymphoid-specific as well as T lineage-specific nuclear factors are involved to differentially form CSB-bound complexes in extracts of various tissues and cell lines. In addition, certain CSB-binding factors were shown to be expressed in a developmental stage-specific fashion. These factors were easily detected in adult thymic extracts but barely in fetal thymic extracts, or vise versa. Similarly, certain factors involved in forming CSB-bound complexes were expressed in CD4+CD8+ immature T cell as well as CD4+ and CD8+ mature lymphocytes, but were barely detectable in immature CD4-CD8- thymocytes. Furthermore, CSB - bound complexes were formed in extracts of mouse fetal brain and liver tissues; however they were absent in extracts of adult''s brain and liver tissues. The results obtained from these studies also showed that transcription factor Oct-1 as well as lymphoid-specific DNA-binding factors Oct-2 and GATA-3 were indeed involved in interacting with CSB both in vivo as demonstrated by a chromatin immunoprecipitation assay and in vitro as evidenced by electrophoretic mobility shift assays in the mouse thymus. Finally, nuclear extracts from chicken tissues were shown to contain the activity of forming tissue-specific CSB-bound complexes similar to that observed in mouse, and the transcription factors GATA-3 and Oct-2 that have been highly conserved during vertebrate evolution were shown to be involved in forming in vitro CSB-bound complexes in chicken. These findings strongly suggest that CSB is a cis-regulatory element which may play a role of regulating the chromatin structure in the TCR Jα region flanking CSB, so that the V to Jα rearrangement in this region could be temporally regulated during T cell development. These results also suggest that further identification of these CSB-interacting factors would help understand the molecular mechanism involved in regulating the rearrangement and expression of genes in TCR α/δ locus during T cell development.
封面
目錄
圖表目錄
中文摘要
英文摘要
縮寫表
壹、緒論
第一節T細胞及T細胞接受器之簡介
一、T細胞的功能與特性
二、T細胞接受器(T cell receptor;TCR)之簡介
第二節V(D)J重組(V(D)J recombination)
一、簡介
二、反應機制(Reaction Mechanism)
三、酵素機構(Enzymatic Machinery)
第三節T細胞接受器基因的重組和表現(Rearrangement and Ezpression of T Cell Receptor Genes)
一、基因重組及表現具血源特異性(Lineage-Specificity)
二、T細胞接受器基因重組及表現具發育時期特異性(Developmental Stage Specificity)
三、有次序性的基因重組及表現(Ordered Rearrangement and Expression)
第四節T細胞接受器α/δ基因座(α/δlocus)與其基因重組及表現
一、α/δ基因座簡介
二、α/δ基因座基因重組及表現的特性
第五節T細胞接受器基因表現之調控
一、T細胞接受器基因之轉錄調控(Transcriptional Regulation of T Cell Receptor Genes)
二、T細胞接受器基因組合之調控(Regulation of rhe Assembly of TCR Genes)
第六節CSB(Conserved Sequence Block)之簡介
第七節研究方向與策略
貳、實驗材料與方法
參、實驗結果
第一部份CSB生化特性之研究
一、CSB與T細胞接受器α加強子(TCR α enhancer)之交互作用
二、與CSB專一性交互作用的細胞核反式作用因子(Nuclear Trans-Acting Factors)之鑑定(Identification)
三、CSB序列中蛋白質因子結合部位之剖析
四、肝臟具有會抑制胸腺CSB-蛋白質複合體生成的因子
五、DNase I腳印(DNase I Footprinting)分析之結果
第二部份CSB結合因子之研究
一、胚胎時期的肝臟、大腦及胸腺具有參與CSB─結合複合體(CSB─binding complexes)形成之蛋白因子
二、胚胎時期的大腦、肝臟及胸腺具有可辨識並結合CSB分段DNA的細胞核因子
三、Gel overlay試驗(gel overlay assays)分析CSB結合因子之表現
四、T細胞的不同發育時期細胞核萃取液CSB結合活性之觀察
五、胚胎時期肝臟細胞核萃取液不會抑制胸腺CSB結合複合體的生成
六、Oct-1、Oct-2、GATA-3等因子參與CSB結合複合體的生成
第三部份小雞CSB結合因子之研究
一、CSB與小雞組織細胞核因子之交互作用
二、CSB分段DNA與小雞組織細胞核因子交互作用
三、Gel Overlay試驗分析小雞CSB結合因子之表現
四、In vitro DNase I腳印試驗之結果
五、GATA-3及Oct-2參與小雞in vitro CSB結合複合體的生成
第四部份未完成實驗部份之初步結果
肆、結論與討論
伍、未來的研究與方向
陸、參考文獻
柒、圖表及附錄p1
陸﹑參考文獻
Afshar, K., Barton, N. R., Hawley, R. S., and Goldstein, L. S. (1995). DNA binding and meiotic chromosomal localization of the Drosophila nod kinesin-like protein. Cell 81, 129-38.
Aguilera, R. J., Akira, S., Okazaki, K., and Sakano, H. (1987). A pre-B cell nuclear protein that specifically interacts with the immunoglobulin V-J recombination sequences. Cell 51, 909-17.
Baumruker, T., Sturm, R., and Herr, W. (1988). OBP100 binds remarkably degenerate octamer motifs through specific interactions with flanking sequences. Genes & Development 2, 1400-13.
Bendall, A. J., Sturm, R. A., Danoy, P. A., and Molloy, P. L. (1993). Broad binding-site specificity and affinity properties of octamer 1 and brain octamer-binding proteins. European Journal of Biochemistry 217, 799-811.
Blackwell, T. K., Moore, M. W., Yancopoulos, G. D., Suh, H., Lutzker, S., Selsing, E., and Alt, F. W. (1986). Recombination between immunoglobulin variable region gene segments is enhanced by transcription. Nature 324, 585-9.
Blunt, T., Finnie, N. J., Taccioli, G. E., Smith, G. C., Demengeot, J., Gottlieb, T. M., Mizuta, R., Varghese, A. J., Alt, F. W., Jeggo, P. A., and et al. (1995). Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 80, 813-23.
Bories, J. C., Demengeot, J., Davidson, L., and Alt, F. W. (1996). Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility. Proceedings of the National Academy of Sciences of the United States of America 93, 7871-6.
Born, W., Yague, J., Palmer, E., Kappler, J., and Marrack, P. (1985). Rearrangement of T-cell receptor beta-chain genes during T-cell development. Proceedings of the National Academy of Sciences of the United States of America 82, 2925-9.
Botfield, M. C., Jancso, A., and Weiss, M. A. (1992). Biochemical characterization of the Oct-2 POU domain with implications for bipartite DNA recognition. Biochemistry 31, 5841-8.
Boubnov, N. V., Hall, K. T., Wills, Z., Lee, S. E., He, D. M., Benjamin, D. M., Pulaski, C. R., Band, H., Reeves, W., Hendrickson, E. A., and et al. (1995). Complementation of the ionizing radiation sensitivity, DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen. Proceedings of the National Academy of Sciences of the United States of America 92, 890-4.
Bouvier, G., Watrin, F., Naspetti, M., Verthuy, C., Naquet, P., and Ferrier, P. (1996). Deletion of the mouse T-cell receptor beta gene enhancer blocks alphabeta T-cell development. Proceedings of the National Academy of Sciences of the United States of America 93, 7877-81.
Capone, M., Watrin, F., Fernex, C., Horvat, B., Krippl, B., Wu, L., Scollay, R., and Ferrier, P. (1993). TCR beta and TCR alpha gene enhancers confer tissue- and stage-specificity on V(D)J recombination events. EMBO Journal 12, 4335-46.
Chen, J., Young, F., Bottaro, A., Stewart, V., Smith, R. K., and Alt, F. W. (1993). Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus. EMBO Journal 12, 4635-45.
Chien, Y. H., Iwashima, M., Wettstein, D. A., Kaplan, K. B., Elliott, J. F., Born, W., and Davis, M. M. (1987). T-cell receptor delta gene rearrangements in early thymocytes. Nature 330, 722-7.
Chung, J. H., Whiteley, M., and Felsenfeld, G. (1993). A 5'' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74, 505-14.
Clevers, H., and Ferrier, P. (1998). Transcriptional control during T-cell development. Current Opinion in Immunology 10, 166-71.
Cooper, M. D., Chen, C. L., Bucy, R. P., and Thompson, C. B. (1991). Avian T cell ontogeny. Advances in Immunology 50, 87-117.
Davis, M. M. (1990). T cell receptor gene diversity and selection. Annual Review of Biochemistry 59, 475-96.
Davis, M. M., and Bjorkman, P. J. (1988). T-cell antigen receptor genes and T-cell recognition [published erratum appears in Nature 1988 Oct 20;335(6192):744]. Nature 334, 395-402.
de Villartay, J. P., Lewis, D., Hockett, R., Waldmann, T. A., Korsmeyer, S. J., and Cohen, D. I. (1987). Deletional rearrangement in the human T-cell receptor alpha-chain locus. Proceedings of the National Academy of Sciences of the United States of America 84, 8608-12.
Dedon, P. C., Soults, J. A., Allis, C. D., and Gorovsky, M. A. (1991). Formaldehyde cross-linking and immunoprecipitation demonstrate developmental changes in H1 association with transcriptionally active genes. Molecular & Cellular Biology 11, 1729-33.
Diaz, P., Cado, D., and Winoto, A. (1994). A locus control region in the T cell receptor alpha/delta locus. Immunity 1, 207-17.
Dudley, E. C., Girardi, M., Owen, M. J., and Hayday, A. C. (1995). Alpha beta and gamma delta T cells can share a late common precursor. Current Biology 5, 659-69.
Elliott, J. F., Rock, E. P., Patten, P. A., Davis, M. M., and Chien, Y. H. (1988). The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature 331, 627-31.
Engler, P., Weng, A., and Storb, U. (1993). Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate. Molecular & Cellular Biology 13, 571-7.
Fitzsimmons, D., and Hagman, J. (1996). Regulation of gene expression at early stages of B-cell and T-cell differentiation. Current Opinion in Immunology 8, 166-74.
Fowlkes, B. J., and Pardoll, D. M. (1989). Molecular and cellular events of T cell development. Advances in Immunology 44, 207-64.
Garman, R. D., Doherty, P. J., and Raulet, D. H. (1986). Diversity, rearrangement, and expression of murine T cell gamma genes. Cell 45, 733-42.
Gerasimova, T. I., and Corces, V. G. (1996). Boundary and insulator elements in chromosomes. Current Opinion in Genetics & Development 6, 185-92.
Giese, K., Kingsley, C., Kirshner, J. R., and Grosschedl, R. (1995). Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. Genes & Development 9, 995-1008.
Gill, L. L., Zaninetta, D., and Karjalainen, K. (1991). A transcriptional enhancer of the mouse T cell receptor delta gene locus. European Journal of Immunology 21, 807-10.
Glimcher, L. H., and Singh, H. (1999). Transcription factors in lymphocyte development--T and B cells get together. Cell 96, 13-23.
Gobel, T. W., Chen, C. L., Lahti, J., Kubota, T., Kuo, C. L., Aebersold, R., Hood, L., and Cooper, M. D. (1994). Identification of T-cell receptor alpha-chain genes in the chicken. Proceedings of the National Academy of Sciences of the United States of America 91, 1094-8.
Godfrey, D. I., Kennedy, J., Mombaerts, P., Tonegawa, S., and Zlotnik, A. (1994). Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. Journal of Immunology 152, 4783-92.
Goldman, J. P., Spencer, D. M., and Raulet, D. H. (1993). Ordered rearrangement of variable region genes of the T cell receptor gamma locus correlates with transcription of the unrearranged genes. Journal of Experimental Medicine 177, 729-39.
Goodhardt, M., Cavelier, P., Doyen, N., Kallenbach, S., Babinet, C., and Rougeon, F. (1993). Methylation status of immunoglobulin kappa gene segments correlates with their recombination potential. European Journal of Immunology 23, 1789-95.
Gottschalk, L. R., and Leiden, J. M. (1990). Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Molecular & Cellular Biology 10, 5486-95.
Grawunder, U., West, R. B., and Lieber, M. R. (1998). Antigen receptor gene rearrangement [see comments]. Current Opinion in Immunology 10, 172-80.
Gstaiger, M., Georgiev, O., van Leeuwen, H., van der Vliet, P., and Schaffner, W. (1996). The B cell coactivator Bob1 shows DNA sequence-dependent complex formation with Oct-1/Oct-2 factors, leading to differential promoter activation. EMBO Journal 15, 2781-90.
Hendrickson, E. A., Qin, X. Q., Bump, E. A., Schatz, D. G., Oettinger, M., and Weaver, D. T. (1991). A link between double-strand break-related repair and V(D)J recombination: the scid mutation. Proceedings of the National Academy of Sciences of the United States of America 88, 4061-5.
Herr, W., and Cleary, M. A. (1995). The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes & Development 9, 1679-93.
Ho, I. C., Bhat, N. K., Gottschalk, L. R., Lindsten, T., Thompson, C. B., Papas, T. S., and Leiden, J. M. (1990). Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. Science 250, 814-8.
Ho, I. C., and Leiden, J. M. (1990). Regulation of the human T-cell receptor alpha gene enhancer: multiple ubiquitous and T-cell-specific nuclear proteins interact with four hypomethylated enhancer elements. Molecular & Cellular Biology 10, 4720-7.
Ho, I. C., and Leiden, J. M. (1990). The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor. Journal of Experimental Medicine 172, 1443-9.
Ho, I. C., Vorhees, P., Marin, N., Oakley, B. K., Tsai, S. F., Orkin, S. H., and Leiden, J. M. (1991). Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. EMBO Journal 10, 1187-92.
Ho, I. C., Yang, L. H., Morle, G., and Leiden, J. M. (1989). A T-cell-specific transcriptional enhancer element 3'' of C alpha in the human T-cell receptor alpha locus. Proceedings of the National Academy of Sciences of the United States of America 86, 6714-8.
Hurwitz, J. L., Samaridis, J., and Pelkonen, J. (1989). Immature and advanced patterns of T cell receptor gene rearrangement among lymphocytes in splenic culture. Journal of Immunology 142, 2533-9.
Ishida, I., Verbeek, S., Bonneville, M., Itohara, S., Berns, A., and Tonegawa, S. (1990). T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proceedings of the National Academy of Sciences of the United States of America 87, 3067-71.
Joulin, V., Bories, D., Eleouet, J. F., Labastie, M. C., Chretien, S., Mattei, M. G., and Romeo, P. H. (1991). A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO Journal 10, 1809-16.
Kirchgessner, C. U., Patil, C. K., Evans, J. W., Cuomo, C. A., Fried, L. M., Carter, T., Oettinger, M. A., and Brown, J. M. (1995). DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267, 1178-83.
Klemm, J. D., Rould, M. A., Aurora, R., Herr, W., and Pabo, C. O. (1994). Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell 77, 21-32.
Koop, B. F., and Hood, L. (1994). Striking sequence similarity over almost 100 kilobases of human and mouse T-cell receptor DNA. Nature Genetics 7, 48-53.
Koop, B. F., Rowen, L., Wang, K., Kuo, C. L., Seto, D., Lenstra, J. A., Howard, S., Shan, W., Deshpande, P., and Hood, L. (1994). The human T-cell receptor TCRAC/TCRDC (C alpha/C delta) region: organization, sequence, and evolution of 97.6 kb of DNA. Genomics 19, 478-93.
Koop, B. F., Wilson, R. K., Wang, K., Vernooij, B., Zallwer, D., Kuo, C. L., Seto, D., Toda, M., and Hood, L. (1992). Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor C alpha/C delta region. Genomics 13, 1209-30.
Korman, A. J., Maruyama, J., and Raulet, D. H. (1989). Rearrangement by inversion of a T-cell receptor delta variable region gene located 3'' of the delta constant region gene. Proceedings of the National Academy of Sciences of the United States of America 86, 267-71.
Kronenberg, M., Siu, G., Hood, L. E., and Shastri, N. (1986). The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annual Review of Immunology 4, 529-91.
Kuo, C. L., Chen, M. L., Wang, K., Chou, C. K., Vernooij, B., Seto, D., Koop, B. F., and Hood, L. (1998). A conserved sequence block in murine and human T cell receptor (TCR) Jalpha region is a composite element that enhances TCR alpha enhancer activity and binds multiple nuclear factors. Proceedings of the National Academy of Sciences of the United States of America 95, 3839-44.
Lauzurica, P., and Krangel, M. S. (1994). Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor delta transgene. Journal of Experimental Medicine 179, 43-55.
Lauzurica, P., and Krangel, M. S. (1994). Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers. Journal of Experimental Medicine 179, 1913-21.
Leiden, J. M. (1993). Transcriptional regulation of T cell receptor genes. Annual Review of Immunology 11, 539-70.
Li, Z., Otevrel, T., Gao, Y., Cheng, H. L., Seed, B., Stamato, T. D., Taccioli, G. E., and Alt, F. W. (1995). The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell 83, 1079-89.
Luo, Y., and Roeder, R. G. (1995). Cloning, functional characterization, and mechanism of action of the B-cell-specific transcriptional coactivator OCA-B. Molecular & Cellular Biology 15, 4115-24.
Marine, J., and Winoto, A. (1991). The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. Proceedings of the National Academy of Sciences of the United States of America 88, 7284-8.
McCormack, W. T., and Thompson, C. B. (1990). Somatic diversification of the chicken immunoglobulin light-chain gene. Advances in Immunology 48, 41-67.
McMurry, M. T., and Krangel, M. S. (2000). A role for histone acetylation in the developmental regulation of VDJ recombination [see comments]. Science 287, 495-8.
Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., and Papaioannou, V. E. (1992). RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869-77.
Oettinger, M. A., Schatz, D. G., Gorka, C., and Baltimore, D. (1990). RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248, 1517-23.
Okada, A., and Alt, F. W. (1994). Mechanisms that control antigen receptor variable region gene assembly. Seminars in Immunology 6, 185-96.
Okada, A., Mendelsohn, M., and Alt, F. (1994). Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells. Journal of Experimental Medicine 180, 261-72.
Passoni, L., Hoffman, E. S., Kim, S., Crompton, T., Pao, W., Dong, M. Q., Owen, M. J., and Hayday, A. C. (1997). Intrathymic delta selection events in gammadelta cell development. Immunity 7, 83-95.
Petrie, H. T., Livak, F., Burtrum, D., and Mazel, S. (1995). T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. Journal of Experimental Medicine 182, 121-7.
Petryniak, B., Staudt, L. M., Postema, C. E., McCormack, W. T., and Thompson, C. B. (1990). Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution. Proceedings of the National Academy of Sciences of the United States of America 87, 1099-103.
Pfeuffer, I., Klein-Hessling, S., Heinfling, A., Chuvpilo, S., Escher, C., Brabletz, T., Hentsch, B., Schwarzenbach, H., Matthias, P., and Serfling, E. (1994). Octamer factors exert a dual effect on the IL-2 and IL-4 promoters. Journal of Immunology 153, 5572-85.
Raulet, D. H. (1989). The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annual Review of Immunology 7, 175-207.
Raulet, D. H., Garman, R. D., Saito, H., and Tonegawa, S. (1985). Developmental regulation of T-cell receptor gene expression. Nature 314, 103-7.
Redondo, J. M., Hata, S., Brocklehurst, C., and Krangel, M. S. (1990). A T cell-specific transcriptional enhancer within the human T cell receptor delta locus. Science 247, 1225-9.
Riegert, P., and Gilfillan, S. (1999). A conserved sequence block in the murine and human TCR J alpha region: assessment of regulatory function in vivo. Journal of Immunology 162, 3471-80.
Roth, M. E., Holman, P. O., and Kranz, D. M. (1991). Nonrandom use of J alpha gene segments. Influence of V alpha and J alpha gene location. Journal of Immunology 147, 1075-81.
Rytkonen, M., Hurwitz, J. L., Tolonen, K., and Pelkonen, J. (1994). Evidence for recombinatorial hot spots at the T cell receptor J alpha locus. European Journal of Immunology 24, 107-15.
Rytkonen, M. A., Hurwitz, J. L., Thompson, S. D., and Pelkonen, J. (1996). Restricted onset of T cell receptor alpha gene rearrangement in fetal and neonatal thymocytes. European Journal of Immunology 26, 1892-6.
Schatz, D. G., Oettinger, M. A., and Baltimore, D. (1989). The V(D)J recombination activating gene, RAG-1. Cell 59, 1035-48.
Schatz, D. G., Oettinger, M. A., and Schlissel, M. S. (1992). V(D)J recombination: molecular biology and regulation. Annual Review of Immunology 10, 359-83.
Schlissel, M. S. (2000). Perspectives: transcription. A tail of histone acetylation and DNA recombination [comment]. Science 287, 438-40.
Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E. M., Stewart, V., Mendelsohn, M., Charron, J., Datta, M., Young, F., Stall, A. M., and et al. (1992). RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855-67.
Sleckman, B. P., Bardon, C. G., Ferrini, R., Davidson, L., and Alt, F. W. (1997). Function of the TCR alpha enhancer in alphabeta and gammadelta T cells. Immunity 7, 505-15.
Sleckman, B. P., Bassing, C. H., Bardon, C. G., Okada, A., Khor, B., Bories, J. C., Monroe, R., and Alt, F. W. (1998). Accessibility control of variable region gene assembly during T-cell development. Immunological Reviews 165, 121-30.
Sleckman, B. P., Gorman, J. R., and Alt, F. W. (1996). Accessibility control of antigen-receptor variable-region gene assembly: role of cis-acting elements. Annual Review of Immunology 14, 459-81.
Smider, V., Rathmell, W. K., Lieber, M. R., and Chu, G. (1994). Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science 266, 288-91.
Snodgrass, H. R., Dembic, Z., Steinmetz, M., and von Boehmer, H. (1985). Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature 315, 232-3.
Snodgrass, H. R., Kisielow, P., Kiefer, M., Steinmetz, M., and von Boehmer, H. (1985). Ontogeny of the T-cell antigen receptor within the thymus. Nature 313, 592-5.
Spencer, D. M., Hsiang, Y. H., Goldman, J. P., and Raulet, D. H. (1991). Identification of a T-cell-specific transcriptional enhancer located 3'' of C gamma 1 in the murine T-cell receptor gamma locus. Proceedings of the National Academy of Sciences of the United States of America 88, 800-4.
Staudt, L. M., Clerc, R. G., Singh, H., LeBowitz, J. H., Sharp, P. A., and Baltimore, D. (1988). Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science 241, 577-80.
Strominger, J. L. (1989). Developmental biology of T cell receptors. Science 244, 943-50.
Taccioli, G. E., and Alt, F. W. (1995). Potential targets for autosomal SCID mutations. Current Opinion in Immunology 7, 436-40.
Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., and Jeggo, P. A. (1994). Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265, 1442-5.
Takeda, J., Cheng, A., Mauxion, F., Nelson, C. A., Newberry, R. D., Sha, W. C., Sen, R., and Loh, D. Y. (1990). Functional analysis of the murine T-cell receptor beta enhancer and characteristics of its DNA-binding proteins. Molecular & Cellular Biology 10, 5027-35.
Thompson, S. D., Manzo, A. R., Pelkonen, J., Larche, M., and Hurwitz, J. L. (1991). Developmental T cell receptor gene rearrangements: relatedness of the alpha/beta and gamma/delta T cell precursor. European Journal of Immunology 21, 1939-50.
Thompson, S. D., Pelkonen, J., and Hurwitz, J. L. (1990). First T cell receptor alpha gene rearrangements during T cell ontogeny skew to the 5'' region of the J alpha locus. Journal of Immunology 145, 2347-52.
Thompson, S. D., Pelkonen, J., Rytkonen, M., Samaridis, J., and Hurwitz, J. L. (1990). Nonrandom rearrangement of T cell receptor J alpha genes in bone marrow T cell differentiation cultures. Journal of Immunology 144, 2829-34.
Ting, C. N., Olson, M. C., Barton, K. P., and Leiden, J. M. (1996). Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384, 474-8.
Tjoelker, L. W., Carlson, L. M., Lee, K., Lahti, J., McCormack, W. T., Leiden, J. M., Chen, C. L., Cooper, M. D., and Thompson, C. B. (1990). Evolutionary conservation of antigen recognition: the chicken T-cell receptor beta chain. Proceedings of the National Academy of Sciences of the United States of America 87, 7856-60.
Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature 302, 575-81.
Tourigny, M. R., Mazel, S., Burtrum, D. B., and Petrie, H. T. (1997). T cell receptor (TCR)-beta gene recombination: dissociation from cell cycle regulation and developmental progression during T cell ontogeny. Journal of Experimental Medicine 185, 1549-56.
Tunnacliffe, A., Sims, J. E., and Rabbitts, T. H. (1986). T3 delta pre-mRNA is transcribed from a non-TATA promoter and is alternatively spliced in human T cells. EMBO Journal 5, 1245-52.
Villey, I., Caillol, D., Selz, F., Ferrier, P., and de Villartay, J. P. (1996). Defect in rearrangement of the most 5'' TCR-J alpha following targeted deletion of T early alpha (TEA): implications for TCR alpha locus accessibility. Immunity 5, 331-42.
Wang, K., Klotz, J. L., Kiser, G., Bristol, G., Hays, E., Lai, E., Gese, E., Kronenberg, M., and Hood, L. (1994). Organization of the V gene segments in mouse T-cell antigen receptor alpha/delta locus. Genomics 20, 419-28.
Waterman, M. L., Fischer, W. H., and Jones, K. A. (1991). A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. Genes & Development 5, 656-69.
Wilson, A., de Villartay, J. P., and MacDonald, H. R. (1996). T cell receptor delta gene rearrangement and T early alpha (TEA) expression in immature alpha beta lineage thymocytes: implications for alpha beta/gamma delta lineage commitment. Immunity 4, 37-45.
Winoto, A., and Baltimore, D. (1989). Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers. Cell 59, 649-55.
Wotton, D., Ghysdael, J., Wang, S., Speck, N. A., and Owen, M. J. (1994). Cooperative binding of Ets-1 and core binding factor to DNA. Molecular & Cellular Biology 14, 840-50.
Yancopoulos, G. D., and Alt, F. W. (1985). Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell 40, 271-81.
Yancopoulos, G. D., and Alt, F. W. (1986). Regulation of the assembly and expression of variable-region genes. Annual Review of Immunology 4, 339-68.
Yancopoulos, G. D., Blackwell, T. K., Suh, H., Hood, L., and Alt, F. W. (1986). Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase. Cell 44, 251-9.
Zhong, X. P., and Krangel, M. S. (1997). An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus. Proceedings of the National Academy of Sciences of the United States of America 94, 5219-24.
Zuniga-Pflucker, J. C., Schwartz, H. L., and Lenardo, M. J. (1993). Gene transcription in differentiating immature T cell receptor(neg) thymocytes resembles antigen-activated mature T cells. Journal of Experimental Medicine 178, 1139-49.
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