title: Transcription outcome of promoters enriched in histone variant H3.3 defined by positioning of H3.3 and local chromatin marks.
abstract: Replication-independent histone variant H3.3 is incorporated into distinct genomic regions including promoters. However topology of promoter-associated H3.3 in relation to chromatin modifications and transcriptional outcome is not known, providing no insight on any distinction between H3.3-containing active and inactive promoters. Here, we report algorithms providing information on gene expression status as a function of density and position of multiple chromatin marks on promoters. We identify a relationship between promoter enrichment in epitope-tagged H3.3 or its canonical isoform H3.2 and corresponding transcriptional outcomes, as a function of sub-promoter positioning of DNA methylation and H3K4me3, H3K9me3 and H3K27me3. We identify a low-frequency configuration of H3.3 and H3K9me3 co-occupancy associated with transcriptional activity, while H3.3 and H3K27me3 promoters are invariably inactive. We unveil H3.3 and DNA methylated promoters whose transcription outcome depends on H3.3 sub-promoter positioning. Our results indicate how spatially restricted positioning of H3.3 may add another layer of transcription regulation.
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
authors.forename: Eivind G
authors.initials: EG
authors.lastname: Lund
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway. Electronic address: erwan.delbarre@medisin.uio.no.
authors.forename: Erwan
authors.initials: E
authors.lastname: Delbarre
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones
keywords: Adipose stem cell; Gene expression; H3.3; Histone modification; Promoter