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XB-ART-53491
Elife March 25, 2014; 3 e01632.

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

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 .


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.

PubMed ID: 24668167
PMC ID: PMC3965291
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: chd1 crebbp ep300 hsp70 nr2e1 prss1 smad1 tab3 taf5


Article Images: [+] show captions
References [+] :
Antonik, Separating structural heterogeneities from stochastic variations in fluorescence resonance energy transfer distributions via photon distribution analysis. 2006, Pubmed