Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and facilitates transcription.

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

https://www.ncbi.nlm.nih.gov/pubmed/24668167

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