PRC1.6复合体表观遗传调控生殖谱系特异性基因的时空表达
收稿日期: 2019-01-27
修回日期: 2019-03-14
网络出版日期: 2019-03-29
基金资助
国家自然科学基金项目(31471233);国家自然科学基金项目(31771447);中央高校基本科研业务费(lzujbky-2017-it51);中央高校基本科研业务费(lzujbky-2018-k05);教育部细胞活动与逆境适应重点实验室开放基金项目(lzujbky-2017-kb05);教育部细胞活动与逆境适应重点实验室开放基金项目(lzujbky-2018-kb05)
Controlling the spatiotemporal expression of germ line specific genes by PRC1.6 complex
Received date: 2019-01-27
Revised date: 2019-03-14
Online published: 2019-03-29
Supported by
the National Natural Science Foundation of China(31471233);the National Natural Science Foundation of China(31771447);the Fundamental Research Funds for the Central Universities(lzujbky-2017-it51);the Fundamental Research Funds for the Central Universities(lzujbky-2018-k05);the Foundation of the Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations(lzujbky-2017-kb05);the Foundation of the Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations(lzujbky-2018-kb05)
多梳抑制复合体1 (polycomb repressive complex 1, PRC1)是一类通过催化和识别染色质表观遗传修饰进而调控基因表达的蛋白复合体,主要参与干细胞干性维持、细胞分化以及细胞周期调控等生理过程,该复合体功能异常影响机体发育或导致癌症发生。在哺乳动物细胞内,PRC1根据组成差异被进一步细分为6种不同的亚型PRC1.1~PRC1.6,它们在靶基因群识别、表观调控机制及生物学功能上存在明显特化。近年来研究发现,PRC1.6复合体在胚胎干细胞及体细胞中对于稳定抑制生殖谱系特异性基因的表达至关重要,同时对于生殖干细胞的干性维持以及精子发生过程中生殖谱系特异性基因的精密调控承担着重要作用。本文在介绍PRC1.6复合体的发现、各组分的分子功能及其参与的生化反应途径的基础上,系统阐述了该复合体在胚胎发育、性腺发育、精子发生等过程中对生殖谱系特异性靶基因群的时空表达发挥的重要调控功能,并探讨了PRC1.6与已知表观遗传调控网络的相互作用,以期为进一步探索生殖谱系基因表达、精子发生的表观遗传调控机制以及男性不育的致病机制提供参考。
孙晓伟,李宏阳,王健,程博 . PRC1.6复合体表观遗传调控生殖谱系特异性基因的时空表达[J]. 遗传, 2019 , 41(4) : 271 -284 . DOI: 10.16288/j.yczz.18-332
Polycomb repressive complex 1 (PRC1) is a class of epigenetic regulatory complexes that normally represses gene expression by catalyzing and/or recognizing chromatin modifications. PRC1 mainly functions in stem cell maintenance, cell differentiation, cell cycle regulation and related processes. PRC1 also have aberrant functions which has been implicated in many types of developmental diseases and cancers. Mammalian PRC1 complexes are divided into six subtypes based on their composition and function; subtypes include PRC1.1 to PRC1.6. Each PRC1 subtype regulates a unique collection of target genes. The PRC1.6 complex subtype plays key roles in specifically repressing transcription of genes controlling germ cell development in embryonic stem cells and other somatic cell types. Recent research demonstrates that the PRC1.6 complex is also crucial for the timely activation of the germ line of specific genes during spermatogenesis, which is essential for proper gonad development. In this review, we summarize the identification of molecular functions of each core component of the PRC1.6 complex including how it recognizes and represses germ line specific genes. We also update the biological roles of this complex in regulating the spatiotemporal expression of germ line specific genes during embryonic development, gonad development, and spermatogenesis. Lastly, the crosstalk between the PRC1.6 complex and the other main epigenetic regulatory mechanisms involved in controlling spermatogenesis is discussed. Our discussion of the PRC1.6 complex in regulating germ line specific genes informs the studies of molecular processes of spermatogenesis and contributes to the understanding of the pathogenic mechanisms of male infertility.
| [1] | Schuettengruber B, Bourbon HM, Di Croce L, Cavalli G . Genome regulation by polycomb and trithorax: 70 years and counting. Cell, 2017,171(1):34-57. |
| [2] | Pasini D, Bracken AP, Helin K . Polycomb group proteins in cell cycle progression and cancer. Cell Cycle, 2004,3(4):396-400. |
| [3] | Lewis EB . A gene complex controlling segmentation in Drosophila. Nature, 1978,276(5688):565-570. |
| [4] | Struhl G . A homoeotic mutation transforming leg to antenna in Drosophila. Nature, 1981,292(5824):635-638. |
| [5] | Geisler SJ, Paro R . Trithorax and polycomb group- dependent regulation: a tale of opposing activities. Development, 2015,142(17):2876-2887. |
| [6] | Ingham PW . Differential expression of bithorax complex genes in the absence of the extra sex combs and trithorax genes. Nature, 1983,306(5943):591-593. |
| [7] | Creppe C, Palau A, Malinverni R, Valero V, Buschbeck M . A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation. PLoS Genet, 2014,10(12):e1004851. |
| [8] | Gao Z, Lee P , Stafford JM, von Schimmelmann M, Schaefer A, Reinberg D. An AUTS2-polycomb complex activates gene expression in the CNS. Nature, 2014,516(7531):349-354. |
| [9] | Morey L, Santanach A, Blanco E, Aloia L, Nora EP, Bruneau BG, Di Croce L . Polycomb regulates mesoderm cell fate-specification in embryonic stem cells through activation and repression mechanisms. Cell Stem Cell, 2015,17(3):300-315. |
| [10] | Margueron R, Li GH, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D . Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell, 2008,32(4):503-518. |
| [11] | Margueron R, Justin N, Ohno K, Sharpe ML, Son J, Drury WJ, Voigt P, Martin SR, Taylor WR, De Marco V, Pirrotta V, Reinberg D, Gamblin SJ . Role of the polycomb protein EED in the propagation of repressive histone marks. Nature, 2009,461(7265):762-767. |
| [12] | Buchwald G, van der Stoop P, Weichenrieder O, Perrakis A, van Lohuizen M, Sixma TK . Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1B. Embo J, 2006,25(11):2465-2474. |
| [13] | Li ZZ, Cao R, Wang M, Myers MP, Zhang Y, Xu RM . Structure of a Bmi1-Ring1b polycomb group ubiquitin ligase complex. J Biol Chem, 2006,281(29):20643-20649. |
| [14] | de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, Koseki H, Brockdorff N . Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell, 2004,7(5):663-676. |
| [15] |