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Mol Cell. 2016 Jul 7;63(1):167-78. doi: 10.1016/j.molcel.2016.05.032. Epub 2016 Jun 30.

Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals.

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  • 1Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
  • 2Department of Mathematical Modeling, Statistics, and Bioinformatics, University of Ghent, Ghent 9000, Belgium.
  • 3Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA. Electronic address: flchedin@ucdavis.edu.

Abstract

R-loops are three-stranded nucleic acid structures formed upon annealing of an RNA strand to one strand of duplex DNA. We profiled R-loops using a high-resolution, strand-specific methodology in human and mouse cell types. R-loops are prevalent, collectively occupying up to 5% of mammalian genomes. R-loop formation occurs over conserved genic hotspots such as promoter and terminator regions of poly(A)-dependent genes. In most cases, R-loops occur co-transcriptionally and undergo dynamic turnover. Detailed epigenomic profiling revealed that R-loops associate with specific chromatin signatures. At promoters, R-loops associate with a hyper-accessible state characteristic of unmethylated CpG island promoters. By contrast, terminal R-loops associate with an enhancer- and insulator-like state and define a broad class of transcription terminators. Together, this suggests that the retention of nascent RNA transcripts at their site of expression represents an abundant, dynamic, and programmed component of the mammalian chromatin that affects chromatin patterning and the control of gene expression.

PMID:
27373332
PMCID:
PMC4955522
[Available on 2017-07-07]
DOI:
10.1016/j.molcel.2016.05.032
[PubMed - in process]
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