title: Sense and antisense transcription are associated with distinct chromatin architectures across genes.
abstract: Genes from yeast to mammals are frequently subject to non-coding transcription of their antisense strand; however the genome-wide role for antisense transcription remains elusive. As transcription influences chromatin structure, we took a genome-wide approach to assess which chromatin features are associated with nascent antisense transcription, and contrast these with features associated with nascent sense transcription. We describe a distinct chromatin architecture at the promoter and gene body specifically associated with antisense transcription, marked by reduced H2B ubiquitination, H3K36 and H3K79 trimethylation and increased levels of H3 acetylation, chromatin remodelling enzymes, histone chaperones and histone turnover. The difference in sense transcription between genes with high or low levels of antisense transcription is slight; thus the antisense transcription-associated chromatin state is not simply analogous to a repressed state. Using mutants in which the level of antisense transcription is reduced at GAL1, or altered genome-wide, we show that non-coding transcription is associated with high H3 acetylation and H3 levels across the gene, while reducing H3K36me3. Set1 is required for these antisense transcription-associated chromatin changes in the gene body. We propose that nascent antisense and sense transcription have fundamentally distinct relationships with chromatin, and that both should be considered canonical features of eukaryotic genes.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Struan C
authors.initials: SC
authors.lastname: Murray
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Haenni
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Françoise S
authors.initials: FS
authors.lastname: Howe
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Fischl
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Karolina
authors.initials: K
authors.lastname: Chocian
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Anitha
authors.initials: A
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK jane.mellor@bioch.ox.ac.uk.
authors.forename: Jane
authors.initials: J
authors.lastname: Mellor
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D005686:Galactokinase / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000096:biosynthesis*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D056488:Histone Chaperones; D006657:Histones; D009707:Nucleosomes; D016372:RNA, Antisense; D029701:Saccharomyces cerevisiae Proteins; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase