多梳家族蛋白

多梳家族蛋白(英语:Polycomb-group proteins)是在果蝇中首次发现的能够重塑染色质从而使基因表观遗传上沉默的一类蛋白质家族。多梳家族蛋白因其可在黑腹果蝇胚胎发育过程中通过调整染色质结构沉默同源异形基因而著名[1]

昆虫中

果蝇属英语Drosophila三胸家族英语Trithorax-group proteins(trxG)与多梳家族(PcG)蛋白的作用是相互拮抗的,他们都与被称为细胞记忆模块英语Cellular Memory Modules(CMMs)的染色体元件发生相互作用。三胸家族(trxG)蛋白维持着基因表达的活性状态,多梳家族(PcG)蛋白通过抑制染色体活性而对冲这种激活作用,这种抑制功能在多个细胞世代中一直保持稳定,只能通过生殖细胞分化过程才能得到逆转。多梳基因复合物所介导的沉默至少需要三类多蛋白复合物:PRC1(多梳抑制复合物1)、PRC2PhoRC。这些复合物共同作用才能达到抑制的效果。

哺乳动物中

多梳家族的基因表达在哺乳动物中对发育的多个方面有着重要作用[2]Bmi1多梳RING指结构域蛋白促使神经干细胞自我更新[3][4]。鼠科PRC2基因的无效突变体会导致胚胎死亡,但大多数PRC1的突变体则生下来就是同源异形突变体,后者导致围生期死亡。相反的是PcG蛋白过表达会与多种肿瘤的严重程度和侵袭力成正相关[5]。哺乳动物的PRC1核心复合物与果蝇的非常相似。已知多梳Bmi1可调ink4基因座p16Ink4ap19Arf[3][6]

植物中

 
多梳基因FIE在未受精卵(右)中表达(蓝色);但在正处于发育过程的二倍孢子体(左)中表达终止。

PcG蛋白FIE在小立碗藓英语Physcomitrella patens中特异性表达于如未受精卵细胞等的干细胞中,这一点通过组织化学GUS染色后显示出的蓝色进行识别。在受精后的早期胚胎FIE基因很快失活[7][8]

对于哺乳动物中:保持细胞处于分化状态来说,PcG是必不可少的;植物中则不是这样的:继发地缺失PcG会导致去分化,促进胚胎发育[9]

多梳家族蛋白通过沉默开花基因座C基因而干扰其对开花的控制[10]。开花基因座C基因是植物中抑制开花通路中的关键环节,在冬季该基因是被沉默的,这被认为是干扰植物春化现象的主要因素[11]

参考文献

  1. ^ Portoso M, Cavalli G. The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming. Morris KV (编). RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press. 2008: 29–44 [2013-11-03]. ISBN 978-1-904455-25-7. (原始内容存档于2014-01-02). 
  2. ^ Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLOS Genetics. 2008, 4 (10): e1000242 [2013-11-03]. PMID 18974828. doi:10.1371/journal.pgen.1000242. (原始内容存档于2015-01-11). 
  3. ^ 3.0 3.1 Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes & Development. 2005, 19 (12): 1432–1437 [2013-11-03]. PMC 1151659 . PMID 15964994. doi:10.1101/gad.1299505. (原始内容存档于2021-05-25). 
  4. ^ Park IK, Morrison SJ, Clarke MF. Bmi1, stem cells, and senescence regulation. Journal of Clinical Investigation. 2004, 113 (2): 175–179 [2013-11-03]. PMC 311443 . PMID 14722607. doi:10.1172/JCI20800. (原始内容存档于2020-07-28). 
  5. ^ Sauvageau M, Sauvageau G. Polycomb group genes: keeping stem cell activity in balance. PLoS Biol. April 2008, 6 (4): e113. PMC 2689701 . PMID 18447587. doi:10.1371/journal.pbio.0060113. 
  6. ^ Popov N, Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health (PDF). EPIGENETICS. 2010, 5 (8): 685–690 [2013-11-03]. PMC 3052884 . PMID 20716961. doi:10.4161/epi.5.8.12996. (原始内容存档于2020-05-11). 
  7. ^ Mosquna A, Katz A, Decker EL, Rensing SA, Reski R, Ohad N. Regulation of stem cell maintenance by the Polyclmb protein FIE has been conserved during land plant evolution. Development. July 2009, 136 (14): 2433–44. PMID 19542356. doi:10.1242/dev.035048. 
  8. ^ The Polycomb gene FIE is expressed (blue) in unfertilised egg cells of the moss Physcomitrella patens (right) and expression ceases after fertilisation in the developing diploid sporophyte (left). In situ GUS staining of two female sex organs (archegonia) of a transgenic plant expressing a translational fusion of FIE-uidA under control of the native FIE promoter. 存档副本. [2009-07-03]. (原始内容存档于2009-06-26). 
  9. ^ Aichinger E, Villar CB, Farrona S, Reyes JC, Hennig L, Köhler C. CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis. PLoS Genet. August 2009, 5 (8): e1000605. PMC 2718830 . PMID 19680533. doi:10.1371/journal.pgen.1000605. 
  10. ^ Jiang D, Wang Y, Wang Y, He Y. Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb repressive complex 2 components. PLoS ONE. 2008, 3 (10): e3404. PMC 2561057 . PMID 18852898. doi:10.1371/journal.pone.0003404. 
  11. ^ Sheldon CC, Rouse DT, Finnegan EJ, Peacock WJ, Dennis ES. The molecular basis of vernalization: the central role of FLOWERING LOCUS C (FLC). Proc. Natl. Acad. Sci. U.S.A. March 2000, 97 (7): 3753–8. PMC 16312 . PMID 10716723. doi:10.1073/pnas.060023597. 

深入阅读

  • Schwartz YB, Pirrotta V. Polycomb silencing mechanisms and the management of genomic programmes. Nat. Rev. Genet. January 2007, 8 (1): 9–22. PMID 17173055. doi:10.1038/nrg1981. 
  • Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G. Genome regulation by polycomb and trithorax proteins. Cell. February 2007, 128 (4): 735–45. PMID 17320510. doi:10.1016/j.cell.2007.02.009. 

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