MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency
2016
Details
Title
MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency
Author(s)
Zhang, Hui ; Gayen, Srimonta ; Xiong, Jie ; Zhou, Bo ; Shanmugam, Avinash K. ; Sun, Yuqing ; Karatas, Hacer ; Liu, Liu ; Rao, Rajesh C. ; Wang, Shaomeng ; Nesvizhskii, Alexey I. ; Kalantry, Sundeep ; Dou, Yali
Published in
Cell Stem Cell
Pagination
14
Volume
18
Issue
4
Pages
481-494
Date
2016
Publisher
Cambridge, Cell Press
ISSN
1934-5909
Keywords
The interconversion between naive and primed; pluripotent states is accompanied by drastic epigenetic; rearrangements. However; it is unclear whether; intrinsic epigenetic events can drive reprogramming; to naive pluripotency or if distinct chromatin states; are instead simply a reflection of discrete pluripotent; states. Here; we show that blocking histone H3K4; methyltransferase MLL1 activity with the small; molecule; inhibitor MM-401 reprograms mouse epiblast; stem cells (EpiSCs) to naive pluripotency. This reversion; is highly efficient and synchronized; with more; than 50% of treated EpiSCs exhibiting features of; naive embryonic stem cells (ESCs) within 3 days. Reverted; ESCs reactivate the silenced X chromosome; and contribute to embryos following blastocyst injection; generating germline; competent chimeras.; Importantly; blocking MLL1 leads to global redistribution; of H3K4me1 at enhancers and represses lineage; determinant factors and EpiSC markers; which; indirectly regulate ESC transcription circuitry. These; findings show that discrete perturbation of H3K4; methylation is sufficient to drive reprogramming to; naive pluripotency.
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Laboratories
ISIC
Record Appears in
Scientific production and competences > SB - School of Basic Sciences > ISIC - Institute of Chemical Sciences and Engineering > UNATTRIBUTED-ISIC - ISIC - Unattributed publications
Peer-reviewed publications
Work produced at EPFL
Journal Articles
Published
Peer-reviewed publications
Work produced at EPFL
Journal Articles
Published
Record creation date
2016-07-19