title: Chromatin signatures at Notch-regulated enhancers reveal large-scale changes in H3K56ac upon activation.
abstract: The conserved Notch pathway functions in diverse developmental and disease-related processes, requiring mechanisms to ensure appropriate target selection and gene activation in each context. To investigate the influence of chromatin organisation and dynamics on the response to Notch signalling, we partitioned Drosophila chromatin using histone modifications and established the preferred chromatin conditions for binding of Su(H), the Notch pathway transcription factor. By manipulating activity of a co-operating factor, Lozenge/Runx, we showed that it can help facilitate these conditions. While many histone modifications were unchanged by Su(H) binding or Notch activation, we detected rapid changes in acetylation of H3K56 at Notch-regulated enhancers. This modification extended over large regions, required the histone acetyl-transferase CBP and was independent of transcription. Such rapid changes in H3K56 acetylation appear to be a conserved indicator of enhancer activation as they also occurred at the mammalian Notch-regulated Hey1 gene and at Drosophila ecdysone-regulated genes. This intriguing example of a core histone modification increasing over short timescales may therefore underpin changes in chromatin accessibility needed to promote transcription following signalling activation.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Lenka
authors.initials: L
authors.lastname: Skalska
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Stojnic
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.affiliation: Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Bettina
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cerda-Moya
authors.affiliation: Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris, France.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris, France.
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.affiliation: Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Russell
authors.affiliation: Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Boris
authors.initials: B
authors.lastname: Adryan
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK sjb32@cam.ac.uk.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bray
mesh_terms: D000107:Acetylation; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics*; D004440:Ecdysone / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C120420:Hey1 protein, mouse; D006657:Histones; C497759:N protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; D014157:Transcription Factors; C099964:lz protein, Drosophila; D004440:Ecdysone; D051548:Histone Acetyltransferases; C524696:nej protein, Drosophila; D050880:p300-CBP Transcription Factors
keywords: CBP/Nejire; CSL; H3K56ac; Notch; chromatin state