Cell Reports
Volume 7, Issue 6, 26 June 2014, Pages 1968-1981
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Article
Otx2 and Oct4 Drive Early Enhancer Activation during Embryonic Stem Cell Transition from Naive Pluripotency

https://doi.org/10.1016/j.celrep.2014.05.037Get rights and content
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Highlights

  • Transcription factor Otx2 drives enhancer activation in differentiating mouse ESCs

  • Oct4 controls Otx2 expression levels

  • Otx2 collaborates with Oct4 in enhancer activation

  • Otx2 contributes to enhancer maintenance and de novo activation

Summary

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, and reciprocally, Otx2 is required for efficient Oct4 recruitment to many enhancer regions. Therefore, the Oct4-Otx2 regulatory axis actively establishes a new regulatory chromatin landscape during the early events that accompany exit from ground state pluripotency.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).