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Cell Rep. 2017 May 16;19(7):1283-1293. doi: 10.1016/j.celrep.2017.04.067.

Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells.

Author information

1
Joan & Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA.
2
Joan & Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10021, USA.
3
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
5
Joan & Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: efa2001@med.cornell.edu.

Abstract

During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner. Temporal degradation of OCT4 during mitotic exit compromises its ability both to maintain and induce pluripotency, suggesting that its regulatory function partly depends on its bookmarking activity. Together, our data document a widespread yet specific bookmarking by histone modifications and transcription factors promoting faithful and efficient propagation of stemness after cell division.

KEYWORDS:

ESCs; H3K27ac; Oct4; bookmarking; cell identity; histone marks; mitosis; reprogramming; stemness; transcription factors

PMID:
28514649
PMCID:
PMC5495017
DOI:
10.1016/j.celrep.2017.04.067
[Indexed for MEDLINE]
Free PMC Article

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