title: Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.
abstract: Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.|Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lavender
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Kimberly R
authors.identifier: 0000-0003-4672-834X
authors.initials: KR
authors.lastname: Cannady
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Jackson A
authors.initials: JA
authors.lastname: Hoffman
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Trotter
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gilchrist
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Bennett
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Burkholder
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, United States of America.|Wexner Medical Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Craig J
authors.identifier: 0000-0002-6899-6751
authors.initials: CJ
authors.lastname: Burd
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Fargo
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Trevor K
authors.initials: TK
authors.lastname: Archer
mesh_terms: D016375:Antisense Elements (Genetics) / Q000096:biosynthesis / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D023281:Genomics; D042421:Histone Code / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic
chemical_list: D016375:Antisense Elements (Genetics); D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes