학술논문

Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells
Document Type
article
Source
Cell Reports, Vol 19, Iss 7, Pp 1283-1293 (2017)
Subject
bookmarking
mitosis
cell identity
stemness
reprogramming
histone marks
transcription factors
Oct4
H3K27ac
ESCs
Biology (General)
QH301-705.5
Language
English
ISSN
2211-1247
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.