Causal role of histone acetylations in enhancer function

ABSTRACT

Enhancers control development and cellular function by spatiotemporal regulation of gene expression. Co-occurrence of acetylation of histone H3 at lysine 27 (H3K27ac) and mono methylation of histone H3 at lysine 4 (H3K4me1) has been widely used for identification of active enhancers. However, increasing evidence suggests that using this combination of marks alone for enhancer identification gives an incomplete picture of the active enhancer repertoire. We have shown that the H3 globular domain acetylations, H3K64ac and H3K122ac, and an H4 tail acetylation, H4K16ac, are enriched at active enhancers together with H3K27ac, and also at a large number of enhancers without detectable H3K27ac. We propose that acetylations at these lysine residues of histones H3 and H4 might function by directly affecting chromatin structure, nucleosome–nucleosome interactions, nucleosome stability, and transcription factor accessibility.

KEYWORDS:

• chromatin
• enhancers
• gene expression
• histone acetylation
• H3 globular domain

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

I thank Wendy Bickmore, Michael Moffat, Rob Schneider, and anonymous reviewers for constructive comments to improve this manuscript.

Funding

I also thank Medical Research Council, UK, University of Essex and Wellcome Trust seed award for funding my work.