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Mol Cell. 2013 Nov 21;52(4):583-90. doi: 10.1016/j.molcel.2013.10.006. Epub 2013 Nov 7.

R loops are linked to histone H3 S10 phosphorylation and chromatin condensation.

Author information

1
Department of Molecular Biology, Universidad de Sevilla-CSIC, Avenida Américo Vespucio, 41092 Seville, Spain.

Abstract

R loops are transcription byproducts that constitute a threat to genome integrity. Here we show that R loops are tightly linked to histone H3 S10 phosphorylation (H3S10P), a mark of chromatin condensation. Chromatin immunoprecipitation (ChIP)-on-chip (ChIP-chip) analyses reveal H3S10P accumulation at centromeres, pericentromeric chromatin, and a large number of active open reading frames (ORFs) in R-loop-accumulating yeast cells, better observed in G1. Histone H3S10 plays a key role in maintaining genome stability, as scored by ectopic recombination and plasmid loss, Rad52 foci, and Rad53 checkpoint activation. H3S10P coincides with the presence of DNA-RNA hybrids, is suppressed by ribonuclease H overexpression, and causes reduced accessibility of restriction endonucleases, implying a tight connection between R loops, H3S10P, and chromatin compaction. Such histone modifications were also observed in R-loop-accumulating Caenorhabditis elegans and HeLa cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics.

PMID:
24211264
DOI:
10.1016/j.molcel.2013.10.006
[Indexed for MEDLINE]
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