OCT4 coordinates with WNT signaling to pre-pattern chromatin at the SOX17 locus during human ES cell differentiation into definitive endoderm

17Citations
Citations of this article
81Readers
Mendeley users who have this article in their library.

Abstract

We demonstrate that the pluripotency gene OCT4 has a role in regulating differentiation via Wnt signaling. OCT4 expression levels in human embryonic stem cells increases transiently during the first 24 hr of in vitro differentiation, with OCT4 occupancy increasing at endoderm regulators such as SOX17 and FOXA2. This increased occupancy correlates with loss of the PRC2 complex and the inhibitory histone mark H3K27me3. Knockdown of OCT4 during differentiation inhibits mesendoderm formation and removal of the H3K27me3 mark from the SOX17 promoter, suggesting that OCT4 acts to induce removal of the PRC2 complex. Furthermore, OCT4 and β-catenin can be co-immunoprecipitated upon differentiation, and Wnt stimulation is required for the enhanced OCT4 occupancy and loss of the PRC2 complex from the SOX17 promoter. In conclusion, our study reveals that OCT4, a master regulator of pluripotency, may also collaborate with Wnt signaling to drive endoderm induction by pre-patterning epigenetic markers on endodermal promoters.

Cite

CITATION STYLE

APA

Ying, L., Mills, J. A., French, D. L., & Gadue, P. (2015). OCT4 coordinates with WNT signaling to pre-pattern chromatin at the SOX17 locus during human ES cell differentiation into definitive endoderm. Stem Cell Reports, 5(4), 490–498. https://doi.org/10.1016/j.stemcr.2015.08.014

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free