title: GC skew is a conserved property of unmethylated CpG island promoters across vertebrates.
abstract: GC skew is a measure of the strand asymmetry in the distribution of guanines and cytosines. GC skew favors R-loops, a type of three stranded nucleic acid structures that form upon annealing of an RNA strand to one strand of DNA, creating a persistent RNA:DNA hybrid. Previous studies show that GC skew is prevalent at thousands of human CpG island (CGI) promoters and transcription termination regions, which correspond to hotspots of R-loop formation. Here, we investigated the conservation of GC skew patterns in 60 sequenced chordates genomes. We report that GC skew is a conserved sequence characteristic of the CGI promoter class in vertebrates. Furthermore, we reveal that promoter GC skew peaks at the exon 1/ intron1 junction and that it is highly correlated with gene age and CGI promoter strength. Our data also show that GC skew is predictive of unmethylated CGI promoters in a range of vertebrate species and that it imparts significant DNA hypomethylation for promoters with intermediate CpG densities. Finally, we observed that terminal GC skew is conserved for a subset of vertebrate genes that tend to be located significantly closer to their downstream neighbors, consistent with a role for R-loop formation in transcription termination.
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, University of California, Davis, CA 95616, United States.
authors.forename: Stella R
authors.initials: SR
authors.lastname: Hartono
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, University of California, Davis, CA 95616, United States.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Korf
authors.affiliation: Department of Molecular and Cellular Biology and Genome Center, University of California, Davis, CA 95616, United States flchedin@ucdavis.edu.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chédin
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D017124:Conserved Sequence; D018899:CpG Islands; D004247:DNA / Q000737:chemistry; D005091:Exons; D005796:Genes; D023281:Genomics; D006801:Humans; D007438:Introns; D051379:Mice; D011401:Promoter Regions, Genetic; D013728:Terminator Regions, Genetic; D014714:Vertebrates / Q000235:genetics*
chemical_list: D004247:DNA