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

TitleWidespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsLiu Y, Pelham-Webb B, Di Giammartino DCampigli, Li J, Kim D, Kita K, Saiz N, Garg V, Doane A, Giannakakou P, Hadjantonakis A-K, Elemento O, Apostolou E
JournalCell Rep
Date Published2017 05 16
KeywordsAcetylation, Animals, Chromatin, Histone Code, Histones, Humans, Lysine, Mitosis, Pluripotent Stem Cells, Proteolysis, Transcription Factors

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.

Alternate JournalCell Rep
PubMed ID28514649
PubMed Central IDPMC5495017
Grant ListDP2 DA043813 / DA / NIDA NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
T32 CA062948 / CA / NCI NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States