title: Bidirectional Transcription Arises from Two Distinct Hubs of Transcription Factor Binding and Active Chromatin.
abstract: Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites (TSSs) near mouse mRNA genes. We find that coupled sense and anti-sense TSSs precisely define the boundaries of a nucleosome-depleted region (NDR) that is highly enriched in transcription factor (TF) motifs. Notably, as the distance between sense and anti-sense TSSs increases, so does the size of the NDR, the level of signal-dependent TF binding, and gene activation. We further discover a group of anti-sense TSSs in macrophages with an enhancer-like chromatin signature. Interestingly, this signature identifies divergent promoters that are activated during immune challenge. We propose that anti-sense promoters serve as platforms for TF binding and establishment of active chromatin to further regulate or enhance sense-strand mRNA expression.
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Scruggs
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gilchrist
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nechaev
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Ginger W
authors.initials: GW
authors.lastname: Muse
authors.affiliation: Center for Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Burkholder
authors.affiliation: Center for Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Fargo
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: adelmank@niehs.nih.gov.
authors.forename: Karen
authors.initials: K
authors.lastname: Adelman
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D016373:DNA, Antisense / Q000235:genetics; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D016373:DNA, Antisense; D009707:Nucleosomes; D012333:RNA, Messenger; D014157:Transcription Factors