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Lysine 5 acetylation of histone H2A associates with cell-type specific regulatory networks in human chromatin

ABSTRACT: The identification of structural determinants of chromatin predicting cell-type, stage- and disease-specific functional networks is a major task of epigenomic studies. Histone post-translational modifications (PTMs) are critical determinants of chromatin accessibility at active cis-regulatory DNA, but they have been found distinctively associated with functional elements only in a few cases. In this study, we have exploited the availability of a validated dataset of promoter and non-promoter Nuclease Accessible Sites (NAS), to dissect through quantitative chromatin immunoprecipitation (qChIP) assays the correlation between 25 histone PTMs and cis-regulatory DNA. Our data show that a combinatorial pattern of histone PTMs is associated mainly with human promoters, and that lysine 5 acetylation of histone H2A (H2AK5ac) is found at functional elements independently from their genomic position. Genome-wide experiments (both ChIP-chip and ChIP-seq were employed) revealed a preferential association of H2AK5ac, and not of its tri-acetylated variant H2A.Z (K4+K7+K11Ac), with CpG islands, DNaseI-hypersensitive sites (DHS) and sites of mono-methylation of lysine 4 of histone H3 (H3K4me1). We demonstrate that H2AK5ac distribution well correlates with active gene expression, in a cell-type and stage-specific manner. Modulation of H2AK5ac during cell differentiation often occurs at sites of H3K4me1, and allowed the localization of developmentally regulated enhancers as well as large-scale chromosomal transitions. Genomic distribution and functional studies showed that H2AK5ac is partially dependent on, but not limited to the enhancer-binding acetyl-transferase p300. Analysis of inducible H2AK5ac sites allowed the computational prediction of binding to enhancer regions by transcription factors regulating cell fate and tumor suppression, which was then experimentally validated. Our findings provide further insights into the functional links between chromatin accessibility and histone PTMs at cis-regulatory elements during biological processes, and pinpoint H2AK5ac as a novel marker for the functional annotation of the epigenome, in a simple and cost-effective manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE16635 | GEO | 2024/12/31

REPOSITORIES: GEO

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Lysine 5 acetylation of histone H2A associates with cell-type specific regulatory networks in human chromatin

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