User:David Benjamin Nyer/Notebook/Nyer Lit Review/2015/09/24

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Owwnotebook icon.png Roles of the Polycomb group proteins in stem cells and cancer Report.pngMain project page

Citation

Cell Death and Disease (2011) 2, e204; doi:10.1038/cddis.2011.84

Summary

PRC1 and PRC2 overview (pages 1-2)

  • Two major complexes - Polycomb-repressive complex 1 (PRC1) and PRC2. PRC2 is typically involved in recruiting PRC1 to promoters of their target genes. Both have been shown to independently silence genes.
  • PRC2 contains EZH2, a histone methyltransferase (HMT) that trimethylates H3K27. H3K27me3 mark often found in promoter regions of developmental genes, represses those genes.
  • H3K27me3 is binding site for chromobox (CBX) domain of proteins, which act as subunits of PRC1. PRC1 then monoubiquitylates H2AK119 by ring domain-containing proteins, RING1B and Bmi-1.
  • monoubiquitin mark is a common epigenetic modification, correlates with chromatin condensation, maintenance of gene silencing. PRC1 itself contributes to the chromatin condensation, ubiquitin residue acts as a platform for transcriptional activation.
  • PRC1 blocks transcriptional elongation of Pol II at bivalent genes (have both repressive and activating trimethyl marks (H3K27me3, H3K4me3)). RNA Pol II pauses within gene body, ready to be activated if signal changes.
  • PRCs also interact with DNA methylation system. EZH2 in PRC2 interacts with DNA methyltransferases (DNMTs). PRCs often recruited by transcription factors that regulate cell fate along with DNMTs.
  • polycomb targets include tumor suppressor genes (p14, p15, p16 at loci CDKN2A and CDKN2B). EZH2 represses expression of DAB2-interacting protein, prohibiting apoptosis. Also represses E2F1 target Bim
  • Trithorax group (TrxG) proteins counteract function of polycomb proteins, activating genes by trimethylating H3K4.

PRCs and Embryonic Stem (ES) cells (pages 2-3)