The chromatin fingerprint of gene enhancer elements

Abstract

Different cell types within a single organism are generally distinguished by strikingly different patterns of gene expression, which are dynamic throughout development and adult life. Distal enhancer elements are key drivers of spatiotemporal specificity in gene regulation. Often located tens of kilobases from their target promoters and functioning in an orientation-independent manner, the identification of bona fide enhancers has proved a formidable challenge. With the development of ChIP-seq, global cataloging of putative enhancers has become feasible. Here, we review the current understanding of the chromatin landscape at enhancers and how these chromatin features enable robust identification of tissue-specific enhancers.

FIGURE 1.

Hypothetical model for establishment of enhancer chromatin states. An enhancer is occupied by non-H3K4-modified nucleosomes prior to stimulus. Upon differentiation or stimulus, H3K4me1/2 is acquired on these nucleosomes, which in turn promotes binding of a pioneer factor. The pioneer factor promotes nucleosome remodeling either by facilitating nucleosome sliding to expose enhancer DNA (59) or by promoting histone exchange to establish labile H3.3/H2A.Z nucleosomes, which are present at “nucleosome-free” regulatory elements (52). This chromatin remodeling facilitates access of general enhancer-binding proteins (i.e. P300 (20)) and additional factors involved in the establishment of different enhancer states. At active enhancers (left), P300 acetylates H3K27, H3K36 is trimethylated, and pol II binds and produces ncRNA. At intermediate enhancers (center), P300 is bound, but H3K27 is not acetylated. At poised enhancers (right), Polycomb proteins are bound and establish H3K27me3, and SETDB1 may also trimethylate H3K9.