Chromatin state maps: new technologies, new insights

Abstract

Recent years have seen unprecedented characterization of mammalian chromatin thanks to advances in chromatin assays, antibody development and genomics. Genome-wide maps of chromatin state can now be readily acquired using microarrays or next-generation sequencing technologies. These datasets reveal local and long-range chromatin patterns that offer insight into the locations and functions of underlying regulatory elements and genes. These patterns are dynamic across developmental stages and lineages. Global studies of chromatin in embryonic stem cells have led to intriguing hypotheses regarding Polycomb/trithorax and RNA polymerase roles in 'poising' transcription. Chromatin state maps thus provide a rich resource for understanding chromatin at a 'systems level', and a starting point for mechanistic studies aimed at defining epigenetic controls that underlie development.

A histone demethylase is necessary for regeneration in zebrafish

“…2C), contain a bivalent me 3 K4/ me 3 K27 H3 chromatin modification. This is consistent with the notion that this chromatin landmark is an indicator of genes that are poised for activation in response to developmental or environmental cues (6,10,(15)(16)(17)(18)(19)(20).…”

“…Notably, several loci, including bmp2a, wnt5a, and sp8, maintained relatively high levels of me 3 K27 H3 during regeneration, and, as such represent cases in which the bivalent domain fails to resolve to monovalent me 3 K4 H3. This phenomena has also been reported in select cases in ES cells (6,15), and is likely to represent an additional layer of complexity with respect to chromatin structure and the regulation of transcription. As opposed to silencing me 3 K27 H3 modifications, the presence of me 3 K4 H3 at transcription start sites typically correlates with transcription activation (6)(7)(8).…”

“…Our observations reinforce the idea that the presence of bivalent me 3 K4/me 3 K27 H3 is not ES cell or stem cell specific. As such, the modification may act to maintain loci in a dormant state with the potential for activation and this may occur in a array of cell types (15,17,20,(32)(33)(34)(35)(36).…”

“…Nucleosomes near the transcription start sites of these silenced loci are decorated with trimethyl lysine 27 histone H3 (me 3 K27 H3) catalyzed by the polycomb repressive complex 2, PRC2 (8,14). In some cases both trimethyl lysine 4 histone H3 (me 3 K4 H3), a product of TrX activity, and me 3 K27 H3 are observed at transcription start sites of developmental regulatory genes, thus creating a ''bivalent'' histone code that appears to poise these loci for activation in ES cells (6,10,15,16). However, it has been suggested that the presence of bivalent chromatin is not indicative of cell multipotency or ''stemness'' (6,(17)(18)(19)(20).…”

Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs

“…In addition, a growing body of evidence points to the influence of unique chromatin state on transcription programs in cell fate specification [19,20]. Interestingly, PRC2, responsible for the generation of repressive histone mark H3K27me3, and core pluripotency factors (OCT4, SOX2 and NANOG) were shown to co-occupy a significant proportion of developmental genes in hESCs [21], suggesting a link between the binding of pluripotency factors and the deposition of H3K27me3.…”