title: Divergent transcription from active promoters.
abstract: Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site-associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisense and sense short RNAs at 250 nucleotides upstream and 50 nucleotides downstream of TSSs, respectively. Northern analysis shows that TSSa-RNAs are subsets of an RNA population 20 to 90 nucleotides in length. Promoter-associated RNAPII and H3K4-trimethylated histones, transcription initiation hallmarks, colocalize at sense and antisense TSSa-RNA positions; however, H3K79-dimethylated histones, characteristic of elongating RNAPII, are only present downstream of TSSs. These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation.
authors.affiliation: Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Seila
authors.forename: J Mauro
authors.initials: JM
authors.lastname: Calabrese
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Levine
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.forename: Peter B
authors.initials: PB
authors.lastname: Rahl
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Flynn
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D016372:RNA, Antisense; D014157:Transcription Factors; D012313:RNA