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Acetylation at the lateral surface of the nucleosome at lysine 64 of H3 regulates chromatin dynamics and defines transcriptionally active chromatin

ABSTRACT: Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. Yet our understanding of how histone modifications directly affect chromatin function remains limited. Here, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation site on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome dynamics by (i) destabilizing nucleosomes, and (ii) regulating chromatin remodelling. Both of these functions have the potential to regulate gene expression. In line with this, we show that the p300 co-activator acetylates H3K64 both in vitro and in vivo. H3K64ac is enriched at the transcriptional start sites (TSS) of active genes and defines transcriptionally active chromatin in ES cells. Moreover, we find that H3K64ac is dynamic during developmental reprogramming, and during mammalian spermatogenesis where H3K64 hyperacetylation precedes histone replacement. Consistent with a function in transcriptional activation, 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 in vivo and they demonstrate that lateral surface modifications can define functionally opposing chromatin states.

ORGANISM(S): Mus musculus

PROVIDER: GSE35355 | GEO | 2014/03/18

SECONDARY ACCESSION(S): PRJNA152737

REPOSITORIES: GEO

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Acetylation at the lateral surface of the nucleosome at lysine 64 of H3 regulates chromatin dynamics and defines transcriptionally active chromatin

Project description:Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. Yet our understanding of how histone modifications directly affect chromatin function remains limited. Here, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation site on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome dynamics by (i) destabilizing nucleosomes, and (ii) regulating chromatin remodelling. Both of these functions have the potential to regulate gene expression. In line with this, we show that the p300 co-activator acetylates H3K64 both in vitro and in vivo. H3K64ac is enriched at the transcriptional start sites (TSS) of active genes and defines transcriptionally active chromatin in ES cells. Moreover, we find that H3K64ac is dynamic during developmental reprogramming, and during mammalian spermatogenesis where H3K64 hyperacetylation precedes histone replacement. Consistent with a function in transcriptional activation, 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 in vivo and they demonstrate that lateral surface modifications can define functionally opposing chromatin states. In this study, 2 biological replicate samples for H3K64ac ChIP and one sample of H3K9ac ChIP in mouse emryonic stem cells were analyzed using custom designed Nimblegen HD2.1oligonucleotide tiling arrays.

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