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

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
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.

Graphical abstract

Teaser

During mitosis, cell identity is temporarily challenged. Liu et al. reveal that maintenance and acquisition of stem cell identity rely on persistent binding of key histone modifications and transcription factors on specific sites of mitotic chromatin.


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