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

Publication Type Academic Article
Authors Liu Y, Pelham-Webb B, Di Giammartino D, Li J, Kim D, Kita K, Saiz N, Garg V, Doane A, Giannakakou P, Hadjantonakis A, Elemento O, Apostolou E
Journal Cell Rep
Volume 19
Issue 7
Pagination 1283-1293
Date Published 05/16/2017
ISSN 2211-1247
Keywords Histone Code, Mitosis, Pluripotent Stem Cells, Transcription Factors
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.
DOI 10.1016/j.celrep.2017.04.067
PubMed ID 28514649
PubMed Central ID PMC5495017
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