title: Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription.
abstract: Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states. DOI: http://dx.doi.org/10.7554/eLife.01632.001.
authors.affiliation: Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR, Strasbourg, France.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Cerbo
authors.forename: Fabio
authors.initials: F
authors.lastname: Mohn
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Emilie
authors.initials: E
authors.lastname: Montellier
authors.forename: Salim
authors.initials: S
authors.lastname: Kacem
authors.forename: Philipp
authors.initials: P
authors.lastname: Tropberger
authors.forename: Eleni
authors.initials: E
authors.lastname: Kallis
authors.forename: Monika
authors.initials: M
authors.lastname: Holzner
authors.forename: Leslie
authors.initials: L
authors.lastname: Hoerner
authors.forename: Angelika
authors.initials: A
authors.lastname: Feldmann
authors.forename: Florian Martin
authors.initials: FM
authors.lastname: Richter
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bannister
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mittler
authors.forename: Jens
authors.initials: J
authors.lastname: Michaelis
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Dirk
authors.initials: D
authors.lastname: Schuebeler
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
authors.forename: Sylvain
authors.initials: S
authors.lastname: Daujat
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
mesh_terms: D000107:Acetylation; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D053595:Embryonic Stem Cells / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine; D008297:Male; D008745:Methylation; D051379:Mice; D041681:NIH 3T3 Cells; D058953:Neural Stem Cells / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism; D014982:Xenopus laevis; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D029867:Xenopus Proteins; D050880:p300-CBP Transcription Factors; D008239:Lysine
keywords: acetylation; chromatin; histone