Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription.
Fiche publication
Date publication
mars 2014
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAUJAT Sylvain
Tous les auteurs :
Di Cerbo V, Mohn F, Ryan DP, Montellier E, Kacem S, Tropberger P, Kallis E, Holzner M, Hoerner L, Feldmann A, Richter FM, Bannister AJ, Mittler G, Michaelis J, Khochbin S, Feil R, Schuebeler D, Owen-Hughes T, Daujat S, Schneider R
Lien Pubmed
Résumé
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.
Mots clés
Acetylation, Animals, Chromatin Assembly and Disassembly, Embryonic Stem Cells, metabolism, Histones, chemistry, Humans, Kinetics, Lysine, Male, Methylation, Mice, NIH 3T3 Cells, Neural Stem Cells, metabolism, Nucleic Acid Conformation, Nucleosomes, metabolism, Protein Conformation, Protein Processing, Post-Translational, Protein Stability, Transcription, Genetic, Transcriptional Activation, Transfection, Xenopus Proteins, chemistry, Xenopus laevis, p300-CBP Transcription Factors, metabolism
Référence
Elife. 2014 Mar;3:e01632