Enhancer regions show high histone H3.3 turnover that changes during differentiation.
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.
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Genetics, Harvard Medical School, Boston, United States.
Aimee M
AM
Deaton
Laboratory for Epigenetic Mechanisms, Instituto Gulbenkian de Ciencia, Oeiras, Portugal.
Mariluz
M
Gómez-Rodríguez
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Genetics, Harvard Medical School, Boston, United States.
Jakub
J
Mieczkowski
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Medicine, Harvard Medical School, Boston, United States.
Michael Y
MY
Tolstorukov
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Genetics, Harvard Medical School, Boston, United States.
Sharmistha
S
Kundu
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, United States.
Ruslan I
RI
Sadreyev
Laboratory for Epigenetic Mechanisms, Instituto Gulbenkian de Ciencia, Oeiras, Portugal.
Lars Et
LE
Jansen
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.|Department of Genetics, Harvard Medical School, Boston, United States.
Robert E
0000-0003-3628-4335
RE
Kingston
D000818:Animals; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors
D006657:Histones; D009707:Nucleosomes; D004247:DNA
chromatin; chromosomes; differentiation; genes; histone H3.3; mouse; stem cells; turnover