title: Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals.
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.
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Lionel A
authors.initials: LA
authors.lastname: Sanz
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Stella R
authors.initials: SR
authors.lastname: Hartono
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Yoong Wearn
authors.initials: YW
authors.lastname: Lim
authors.affiliation: Department of Mathematical Modeling, Statistics, and Bioinformatics, University of Ghent, Ghent 9000, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steyaert
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Rajpurkar
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ginno
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, 1 Shields Avenue, University of California, Davis, Davis, CA 95616, USA. Electronic address: flchedin@ucdavis.edu.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chédin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D018388:Codon, Terminator; D019295:Computational Biology; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D006801:Humans; D020014:K562 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D002843:Chromatin; D018388:Codon, Terminator; D012313:RNA; D004247:DNA