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Elife. 2016 Jun 15;5. pii: e15316. doi: 10.7554/eLife.15316.

Enhancer regions show high histone H3.3 turnover that changes during differentiation.

Author information

1
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.
2
Department of Genetics, Harvard Medical School, Boston, United States.
3
Laboratory for Epigenetic Mechanisms, Instituto Gulbenkian de Ciencia, Oeiras, Portugal.
4
Department of Medicine, Harvard Medical School, Boston, United States.
5
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, United States.

Abstract

The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation.

KEYWORDS:

chromatin; chromosomes; differentiation; genes; histone H3.3; mouse; stem cells; turnover

PMID:
27304074
PMCID:
PMC4965263
DOI:
10.7554/eLife.15316
[Indexed for MEDLINE]
Free PMC Article

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