Otx2 and Oct4 Drive Early Enhancer Activation during Embryonic Stem Cell Transition from Naive Pluripotency

Shen Hsi Yang, Tüzer Kalkan, Claire Morissroe, Hendrik Marks, Hendrik Stunnenberg, Austin Smith, Andrew D. Sharrocks

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Embryonic stem cells (ESCs) are unique in that they have the capacity to differentiate into all of the cell types in the body. We know a lot about the complex transcriptional control circuits that maintain the naive pluripotent state under self-renewing conditions but comparatively less about how cells exit from this state in response to differentiation stimuli. Here, we examined the role of Otx2 in this process in mouse ESCs and demonstrate that it plays a leading role in remodeling the gene regulatory networks as cells exit from ground state pluripotency. Otx2 drives enhancer activation through affecting chromatin marks and the activity of associated genes. Mechanistically, Oct4 is required for Otx2 expression, andreciprocally, Otx2 is required for efficient Oct4 recruitment to many enhancer regions. Therefore, the Oct4-Otx2 regulatory axis actively establishes anew regulatory chromatin landscape during the early events that accompany exit from ground state pluripotency.

Original languageEnglish
Pages (from-to)1968-1981
Number of pages14
JournalCell Reports
Volume7
Issue number6
DOIs
Publication statusPublished - 26 Jun 2014
Externally publishedYes

Fingerprint

Dive into the research topics of 'Otx2 and Oct4 Drive Early Enhancer Activation during Embryonic Stem Cell Transition from Naive Pluripotency'. Together they form a unique fingerprint.

Cite this