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. 2020 Oct;10(10):200255.
doi: 10.1098/rsob.200255. Epub 2020 Oct 14.

Establishment and function of chromatin modification at enhancers

Amanuel Tafessu  1 , Laura A Banaszynski  1
Affiliations

Establishment and function of chromatin modification at enhancers

Amanuel Tafessu et al. Open Biol. 2020 Oct.

Abstract

How a single genome can give rise to distinct cell types remains a fundamental question in biology. Mammals are able to specify and maintain hundreds of cell fates by selectively activating unique subsets of their genome. This is achieved, in part, by enhancers-genetic elements that can increase transcription of both nearby and distal genes. Enhancers can be identified by their unique chromatin signature, including transcription factor binding and the enrichment of specific histone post-translational modifications, histone variants, and chromatin-associated cofactors. How each of these chromatin features contributes to enhancer function remains an area of intense study. In this review, we provide an overview of enhancer-associated chromatin states, and the proteins and enzymes involved in their establishment. We discuss recent insights into the effects of the enhancer chromatin state on ongoing transcription versus their role in the establishment of new transcription programmes, such as those that occur developmentally. Finally, we highlight the role of enhancer chromatin in new conceptual advances in gene regulation such as condensate formation.

Keywords: chromatin; enhancer; histone variants; phase separation; post-translational modification; transcription.

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Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
Features of enhancer chromatin. (a) An active enhancer bound by transcription factors (TF) and enriched in H2A.Z/H3.3 nucleosomes (blue), H3K4me1 (magenta) and H3K27ac (green). Histone methyltransferases MLL3/4 catalyse mono-methylation of H3K4, while acetyltransferases CBP/p300 acetylate both histones and transcription factors. (b) Catalytic activities of MLL3/4 and p300 are dispensable for maintaining transcription in embryonic stem cells (green) but are required to drive transcription upon stress response or differentiation. Created with BioRender.com.
Figure 2.
Figure 2.
Regulation of histone acetyltransferase CBP/p300 activity. (a) p300 is subject to activating (yellow—S1834, S2271, S2279, S2291, S2315) and inhibitory (brown—S89) phosphorylation. Upon activation, p300 undergoes a conformational change to displace the RING domain and expose the active site. (b) Phosphorylation (yellow) of Ser31 of H3.3 (blue) nucleosomes stimulates p300 activity (H3K27ac—green) on canonical histones (orange). (c) Stimulus-induced phosphorylation of STAT1 induces p300 dimerization and auto-acetylation (green) of its auto-inhibitory loop (magenta), resulting in p300 activation.
Figure 3.
Figure 3.
Phase separation of transcription machinery. (a) Transcription factors and cofactors with intrinsically disordered regions drive the formation of biomolecular condensates at enhancers. (b) Hypoacetylated nucleosome arrays assembled in vitro spontaneously undergo liquid–liquid phase separation (LLPS). Acetylation by p300 blocks LLPS, while addition of synthetic multi-bromodomain proteins (green) restores biomolecular condensates.
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