Occupying Chromatin: Polycomb Mechanisms for Getting to Genomic Targets, Stopping Transcriptional Traffic, and Staying Put

被引:550
作者
Simon, Jeffrey A. [1 ]
Kingston, Robert E. [2 ,3 ]
机构
[1] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
关键词
RNA-POLYMERASE-II; H3; LYSINE; 27; REPRESSIVE COMPLEX 2; HISTONE METHYLTRANSFERASE ACTIVITY; LONG NONCODING RNA; GROUP CBX FAMILY; GROUP PROTEINS; GENE-EXPRESSION; H2A UBIQUITYLATION; DNA-REPLICATION;
D O I
10.1016/j.molcel.2013.02.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence key developmental regulators and are centrally integrated in the transcriptional circuitry of stem cells. PRC2 trimethylates histone H3 on lysine 27 (H3K27me3), and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs are deployed to select and silence genomic targets is the subject of intense investigation. We review advances on targeting, modulation, and functions of PRC1 and PRC2 and progress on defining the transcriptional steps they impact. Recent findings emphasize PRC1 targeting independent of H3K27me3, nonenzymatic PRC1-mediated compaction, and connections between PRCs and noncoding RNAs. Systematic analyses of Polycomb complexes and associated histone modifications during DNA replication and mitosis have also emerged. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell-cycle progression.
引用
收藏
页码:808 / 824
页数:17
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