Skip to main content
. Author manuscript; available in PMC: 2018 Jun 4.
Published in final edited form as: Nat Genet. 2017 Dec 4;50(1):83–95. doi: 10.1038/s41588-017-0002-y

Figure 7. TET1 and DNMT3B compete to regulate the methylation of the PAX6 P0 bivalent promoter.

Figure 7

In WT hESCs TET1 or 5hmC functions to antagonize DNMT3B at the PAX6 bivalent promoter and prevents DNA hypermethylation. Upon NE differentiation PAX6 expression is activated and leads to the production of PAX6 and SOX1 double positive cells that are negative for the pluripotency marker OCT4. In TKO hESCs increased DNMT3B binding at the PAX6 bivalent promoter leads to increased DNA methylation. As a result PAX6 expression is not activated and ultimately few PAX6 or SOX1-positive cells are produced and a large number of cells still express the pluripotency marker OCT4. Targeted demethylation of the PAX6 P0 bivalent promoter or inactivation of DNMT3B in the TKO background (QKO) reduces methylation at the PAX6 bivalent promoter, allowing activation of PAX6 expression upon differentiation.