dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing
Open Access
- 15 October 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 22 (20) , 2799-2810
- https://doi.org/10.1101/gad.484208
Abstract
Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.Keywords
This publication has 51 references indexed in Scilit:
- Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylationGenes & Development, 2008
- JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genesNature, 2007
- RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair ProteinsCell, 2007
- Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genesThe EMBO Journal, 2007
- Ubiquitylation of histone H2B controls RNA polymerase II transcription elongation independently of histone H3 methylationGenes & Development, 2007
- Genome Regulation by Polycomb and Trithorax ProteinsPublished by Elsevier ,2007
- Structure and E3-ligase activity of the Ring–Ring complex of Polycomb proteins Bmi1 and Ring1bThe EMBO Journal, 2006
- A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activitiesGenes & Development, 2006
- Role of Bmi-1 and Ring1A in H2A Ubiquitylation and Hox Gene SilencingMolecular Cell, 2005
- Role of histone H2A ubiquitination in Polycomb silencingNature, 2004