title: Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.
abstract: Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation.
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Vibhor
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Nirmala Arul
authors.initials: NA
authors.lastname: Rayan
authors.affiliation: Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan; Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Masafumi
authors.initials: M
authors.lastname: Muratani
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Stefan
authors.initials: S
authors.lastname: Lim
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Bavani
authors.initials: B
authors.lastname: Elanggovan
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Lixia
authors.initials: L
authors.lastname: Xin
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Tess
authors.initials: T
authors.lastname: Lu
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Harshyaa
authors.initials: H
authors.lastname: Makhija
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Jeremie
authors.initials: J
authors.lastname: Poschmann
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore; Department of Biology, Clarkson University, Potsdam, New York 13699, USA;
authors.forename: Thomas
authors.initials: T
authors.lastname: Lufkin
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Huck Hui
authors.initials: HH
authors.lastname: Ng
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
authors.forename: Shyam
authors.initials: S
authors.lastname: Prabhakar
mesh_terms: D000107:Acetylation; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones