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R-loops enhance polycomb repression at a subset of developmental regulator genes

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Item Type:Article
Title:R-loops enhance polycomb repression at a subset of developmental regulator genes
Creators Name:Skourti-Stathaki, K. and Torlai Triglia, E. and Warburton, M. and Voigt, P. and Bird, A. and Pombo, A.
Abstract:R-loops are three-stranded nucleic acid structures that form during transcription, especially over unmethylated CpG-rich promoters of active genes. In mouse embryonic stem cells (mESCs), CpG-rich developmental regulator genes are repressed by the Polycomb complexes PRC1 and PRC2. Here, we show that R-loops form at a subset of Polycomb target genes, and we investigate their contribution to Polycomb repression. At R-loop-positive genes, R-loop removal leads to decreased PRC1 and PRC2 recruitment and Pol II activation into a productive elongation state, accompanied by gene derepression at nascent and processed transcript levels. Stable removal of PRC2 derepresses R-loop-negative genes, as expected, but does not affect R-loops, PRC1 recruitment, or transcriptional repression of R-loop-positive genes. Our results highlight that Polycomb repression does not occur via one mechanism but consists of different layers of repression, some of which are gene specific. We uncover that one such mechanism is mediated by an interplay between R-loops and RING1B recruitment.
Keywords:R Loops, Polycomb Proteins, RING1B, Gene Regulation, RNA Polymerase II, Poising, Animals, Mice
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Volume:73
Number:5
Page Range:930-945
Date:7 March 2019
Official Publication:https://doi.org/10.1016/j.molcel.2018.12.016
PubMed:View item in PubMed

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