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1 HEREDITAS (Beijing) , 31(10): ISSN 综述 DOI: /SP.J Polycomb group (PcG) 蛋白复合体马克学 1, 席兴字 1., ; 2., Polycomb group (PcG) 蛋白是一组通过染色质修饰调控靶基因的转录抑制子, 从生化和功能上它可以分成两个主要的核心蛋白复合体 PRC1(Polycomb repressive complex 1) 和 PRC2(Polycomb repressive complex 2) 研究发现 PcG 蛋白不仅控制个体正确的发育模式, 而且与细胞的增殖分化和肿瘤发生有关文章就 PcG 蛋白的组成作用机制及功能进行综述, 并对 PcG 未来的研究方向进行展望 PcG 蛋白 ; 转录抑制 ; 染色质修饰 ; 干细胞 Polycomb group protein complexes MA Ke-Xue 1, XI Xing-Zi 2 1. College of Life Sciences, Henan Normal University, Xinxiang , China; 2. Department of Education Sciences, Xinxiang University, Xinxiang , China Abstract: The transcriptional repressors of the polycomb group (PcG) proteins regulate the targeted genes expression through chromatin modifications. They can be separated biochemically and functionally into two major core multiprotein complexes: PRC1 (Polycomb repressive complex 1) and PRC2 (Polycomb repressive complex 2). Studies revealed that PcG proteins were not only crucial for correct execution of developmental programs but also involved in the regulation of cell proliferation, differentiation, and tumorigenesis. This paper summarizes the components of PcG proteins complexes, its silencing mechanisms and biological functions, and discusses the study of PcG proteins in future. Keywords: PcG proteins; transcriptional repression; chromatin modification; stem cell, Polycomb group(pcg) [1] PcG, Trithorax group (TrxG), [2], PcG X PcG 1 PcG, PcG : Polycomb repressive complex2 (PRC2), ; Polycomb repressive complex1(prc1), [3, 4], PRC2 Extra Sex Combs (ESC) Enhancer of 收稿日期 : ; 修回日期 : 基金项目 : ( 2008qk14), 作者简介 : (1972 ),,,, : Tel: ; makexue@sina.com

2 978 HEREDITAS (Beijing) Zeste [E(z)] 600 kda, Rpd3 (Histone deacetylases, HDAC) PcG Su(z)12 p55/rbap48 [5] PcG,, PRC2 EED EZH2 Su(z)12 RbAp48 AEBP2, AEBP2 PRC1 3 MDa, Pc (Polycomb) Ph (polyhomeotic) Psc (Posterior sex combs) [3] : PRC1 M33/ HPC1 BMI-1 MEL-18 HPH1 HPH2 HPH3 HPC2 HPC3 SCMH1 RING1A RING1B 1 MDa,, PcG [6], PcG PRC1 PRC2, PRC1 PRC2, PSC, PRC1 PRC2, PSC PRC1 [4], PcG PRE (Polycomb response element), PREs, [7] PcG PRE DNA, PRC1 PRC2 DNA, PHO(Pleiohometic) YY1, DNA PcG PHO/YY1 PRC2 EED EZH2, PRC1 PC PH, PHO/YY1 PcG 3, PcG PRE [7] PHO, PcG [8], PHO, PcG DNA GAGA Pipsqueak Zeste Dsp1 Grainyhead Sp1/KLF PcG [5, 7] PcG,, PcG DNA 2 PcG PcG SUV39H Enhancer of zeste Trithorax SET, SUV39H H3-K9 [9] SET, 4 PRC2 E(z)/EZH2 [4], H3-K27, H3-K9 : E(z) PcG, H3-K27 PC PRE, [4] H3-K9 HP1, H3-K27, PcG PC PSC DNA, PRC2 E(z) H3-K27 PcG, PRC1, 3 :, PRC1 DNA ;, PRC1, ;, PRC1 H3-K27, H2B H3-K4 PcG, TrxG H3-K4, [2],,,, EED HDAC1 (Histone deacetylases) HDAC2, EED HDAC, PRC2 HDAC

3 10 : Polycomb group (PcG) 979 RpD3 p55, RpD3 PcG [10], PcG HDAC, PcG RING1B BMI-1 draf dkdm2, H2A -K119 [11] RING1B H2A, H3-K27 H2A RNA pol Ⅱ, [12], PcG, PRC1 ATP SWI/SNF PRC1 TBP, PcG, EZH2 DNA [13], PcG DNA PcG, PcG 3 PcG 3.1 PcG PcG, (Homeotic gene), 3 h,,, (Antennapedia complex, ANT-C) (Bithorax complex, Bx-C) ANT-C labial (lab) proboscipedia (pb) Deformed (Dfd) Sex combs reduced (Scr) Antennapedia (Antp) 5, BX-C Ubx abd-a Abd-B 3, P5 P14, 3 8,, Antp, pb, Scr (Labial) (Maxillary) [14], polycomb trithorax PcG,, trxg PcG [14] trxg PcG, Chang [15] PcG EED EED, EED, PcG [16] 3.2 PcG, PcG [17] (Embryonic stem cell, ES cell),, PcG Ezh2 Eed YY1 Rnf2 [18] Ezh2 Rnf2, Ezh2 Ezh2 ES PRC1 Bmi1 Mel-18 Mph1/Rae28 M33, T B [6, 17, 18] Bmi-1, Molofsky [19] Bmi-1, Bmi-1, Bmi-1 PcG BMI-1 Ink4a/Arf, P16 Ink4a P19 Arf [20] Bmi-1, P16 Ink4a P19 Arf, P16 Ink4a P19 Arf p53 [17, 19]

4 980 HEREDITAS (Beijing) , Ink4a/Arf, E2F6 PcG BMI-1 E2F6 E2F, RB, E2F [20] E2F6 BMI-1, CD34 +, E2F6 PcG p19 Arf [21] HPC2 E2F RB CtBP RING1, RB-E2F G2/M [22] 3.3 PcG X X, X, X (X chromosome inactivation, XCI), PcG X [23] (Extraembryonic tissues), X (Xi), X, eed / X [24] EED EZH2 X, X [25] H3-K27 Xi, PRC2, eed / H3-K27 [25] PcG X, EED, EED X, PRC1 Ring1b [26], PcG X, Xi [23] 4 PcG PcG Beà [27] 25% (Mantle cell lymphoma, MCL) Bmi-1, Bmi-1 Ezh2 PcG, [6, 18, 20] MEL-18 Mel-18 17q,, Mel-18, Mel-18 [6], PcG EZH2 BMI-1 EZH2 BMI-1,, PcG [28], PcG 5, PcG, PcG Hox/Homeotic, PcG PcG, PcG PcG,, PcG, PcG, Shh(Sonic hedgehog) PcG Bmi-1 [29], Shh Wnt Notch PcG, PcG

5 10 : Polycomb group (PcG) 981 参考文献 (References): [1] Terranova R, Yokobayashi S, Stadler MB, Otte AP, Van Lohuizen M, Orkin SH, Peters AH. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell, 2008, 15(5): [2] Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G. Genome regulation by polycomb and trithorax proteins. Cell, 2007, 128(4): [3] Otte AP, Kwaks TH. Gene repression by polycomb group protein complexes: a distinct complex for every occasion? Curr Opin Genet Dev, 2003, 13(5): [4] Lund AH, Lohuizen M. Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol, 2004, 16(3): [5] Schwartz YB, Pirrotta V. Polycomb complexes and epigenetic states. Curr Opin Cell Biol, 2008, 20(3): [6] Lessarda J, Sauvageaua G. Polycomb group genes as epigenetic regulators of normal and leukemic hemopoiesis. Exp Hematol, 2003, 31(7): [7] Kohler C, Villar CBR. Programming if gene expression by polycomb group proteins. Trend Cell Biol, 2008, 18(5): [8] Brown JL, Fritsch C, Mueller J, Kassis JA. The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing. Development, 2003, 130(2): [9] Rea SF, Eisenhaber D, O Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T. Regulation of chromatin structure by sitespecific histone H3 methyltransferases. Nature, 2000, 406(6796): [10] Tie F, Furuyama T, Prasad-Sinha J, Jane E, Harte PJ. The Drosophila polycomb group proteins ESC and E (Z) are present in a complex containing the histone-binding protein p55 and the histone deacetylase RPD3. Development, 2001, 128(2): [11] Muller J, Verrijzer P. Biochemical mechanisms of gene regulation by polycomb group protein complexes. Curr Opin Genet Dev, 2009, 19: 1 9. [12] Dellino GI, Schwartz YB, Farkas G, McCabe D, Elgin SC, Pirrotta V. Polycomb silencing blocks transcription initiation. Mol Cell, 2004, 13(6): [13] Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C. The polycomb group protein EZH2 directly controls DNA methylation. Nature, 2006, 439(7078): [14] Vasanthi D, Mishra RK. Epigenetic regulation of genes during development: A conserved theme from flies to mammals. J Genet Genomics, 2008, 35(7): [15] Chang C, Cox M, Fletcher J. Regulation of early Xenopus development by the polycomb group protein EED. Dev Biol, 2008, 319(2): [16] Kim SN, Jung K, Chung HM, Kim SH, Jeon SH. The pleiohomeotic gene is required for maintaining expression of genes functioning in ventral appendage formation in Drosophila melanogaster. Dev Biol, 2008, 319(1): [17] Takihara Y. Role of polycomb-group genes in sustaining activities of normal and malignant stem cells. Int J Hematol, 2008, 87(1): [18] Valk-Lingbeek ME, Bruggeman SWM, Lohuizen M. Stem cells and cancer: the polycomb connection. Cell, 2004, 118(4): [19] Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, 2003: 425(6961): [20] Jacobs JL, Lohuizen M. Polycomb repression: from cellular memory to cellular proliferation and cancer. Biochim Biophys Acta, 2002, 1602(2): [21] Furukawa Y, Nakamura M, Matsuda M. Transcriptional repressor E2F6 regulates apoptosis of hematopoietic stem cells. Exp Hematol, 2000, 28: [22] Dahiya A, Wong S, Gonzalo S, Gavin M, Dean DC. Linking the Rb and polycomb pathways. Mol Cell, 2001, 8(3): [23] Erwin JA, Lee JT. New twists in X-chromosome inactivation. Curr Opin Cell Biol, 2008, 20(3): [24] Wang J, Mager J, Chen Y, Schneider E, Cross JC, Nagy A, Magnuson T. Imprinted X inactivation maintained by a mouse Polycomb group gene. Nat Genet, 2001, 28(4): [25] Shibata S, Yokota T, Wutz A. Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation. EMBO J, 2008, 27(13): [26] Leeb M, Wutz A. Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. J Cell Biol, 2007, 178(2): [27] Beà S, Tort F, Pinyol M, Puig X, Hernández L, Hernández S, Fernández PL, van Lohuizen M, Colomer D, Campo E. BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res, 2001, 61(6): [28] Schulz WA, Hoffmann MJ. Epigenetic mechanisms in the biology of prostate cancer. Semin Cancer Biol, 2009, 19(3): [29] Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremas-lani P, van Lohuizen M, Marino S. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature, 2004, 428 (6980):

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<4D6963726F736F667420506F776572506F696E74202D20B5DAC1F9D5C220C9FACEEFB5C4B7A2D3FD> 第六章从细胞到个体第七章生物的发育第一节生殖细胞的形成与受精作用第二节胚胎发育过程第三节发育的分子机制生物的生活周期 : 世代交替 (alteration generations): 多细胞生物体的生活史中, 存在双倍体细胞和单倍体细胞