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. 2011 Dec 29;40(8):3364–3377. doi: 10.1093/nar/gkr1253

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Published by Oxford University Press 2011.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 6. — Proposed model for Tet1-mediated epigenetic and transcriptional regulation of mESC self-renewal and pluripotency. Red arrows denote regulatory interactions inferred from data generated for this study. Tet1, regulated by Oct4 (28), regulates DNA methylation (5mC) by converting 5mC to 5hmC (16,28). Tet1 regulates LIF/Stat3 signaling by facilitating Stat3 binding by an yet to be determined mechanism, and regulates the transcriptional regulatory module comprising Nanog, Esrrb, Tcl1, Tbx3, Klf2/4, Prdm14 and Lefty1/2. Tet1's regulation of Tet2 confers tight regulation of 5mC to 5hmC conversion. Tet1's negative regulation of de novo DNA methyltransferase Dnmt3b may provide an additional layer of Tet1-mediated regulation of 5mC. Silent and active promoters on the chromatin are denoted by broad red and green arrows, respectively.