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

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.
Mesh Terms:
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, DNA, Single-Stranded, Genomic Instability, HeLa Cells, Histones, Humans, Meiosis, Mitosis, Open Reading Frames, Phosphorylation, Protein Processing, Post-Translational, RNA Polymerase II, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic
Mol. Cell
Date: Nov. 21, 2013
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