Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells
- 25 November 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 9 (12), 1428-1435
- https://doi.org/10.1038/ncb1663
Abstract
Changes in phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP) are associated with transcription initiation, elongation and termination1,2,3. Sites of active transcription are generally characterized by hyperphosphorylated RNAP, particularly at Ser 2 residues, whereas inactive or poised genes may lack RNAP or may bind Ser 5-phosphorylated RNAP at promoter proximal regions. Recent studies have demonstrated that silent developmental regulator genes have an unusual histone modification profile in ES cells, being simultaneously marked with Polycomb repressor-mediated histone H3K27 methylation, and marks normally associated with gene activity4,5. Contrary to the prevailing view, we show here that this important subset of developmental regulator genes, termed bivalent genes, assemble RNAP complexes phosphorylated on Ser 5 and are transcribed at low levels. We provide evidence that this poised RNAP configuration is enforced by Polycomb Repressor Complex (PRC)-mediated ubiquitination of H2A, as conditional deletion of Ring1A and Ring1B leads to the sequential loss of ubiquitination of H2A, release of poised RNAP, and subsequent gene de-repression. These observations provide an insight into the molecular mechanisms that allow ES cells to self-renew and yet retain the ability to generate multiple lineage outcomes.Keywords
This publication has 30 references indexed in Scilit:
- Epigenetic signatures of stem-cell identityNature Reviews Genetics, 2007
- The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cellsGenes & Development, 2007
- Phosphorylation and functions of the RNA polymerase II CTDGenes & Development, 2006
- Breaking barriers to transcription elongationNature Reviews Molecular Cell Biology, 2006
- Polycomb Repressive Complexes Restrain the Expression of Lineage-Specific Regulators in Embryonic Stem CellsCell Cycle, 2006
- Polycomb complexes repress developmental regulators in murine embryonic stem cellsNature, 2006
- Control of Developmental Regulators by Polycomb in Human Embryonic Stem CellsCell, 2006
- A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem CellsCell, 2006
- Chromatin signatures of pluripotent cell linesNature, 2006
- The CTD codeNature Structural & Molecular Biology, 2003