Nanog mediated control of TBX3-GATA6 circuitry in primitive endoderm differentiation of mESCs
Wu, Hao, Ye, Ying, Dai, Hongxia, Chen, Peixin, Yang, Tenghui, Li, Zhifang, Li, Li, Parsania, Chirag, Ding, Junjun, Zhang, Man, Zuo, Erwei, Schmitz, Ulf, Chen, Xi, Zhu, Zhexin, and Zhang, Wensheng (2026) Nanog mediated control of TBX3-GATA6 circuitry in primitive endoderm differentiation of mESCs. EMBO Reports, 27 (5). pp. 1209-1227.
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Abstract
Cell fate decisions in the early embryo rely on reciprocal transcriptional networks that balance pluripotency with lineage commitment. NANOG is essential for directing the epiblast–primitive endoderm (PrE) fate choice, but the molecular mechanisms underlying its repressive activity remain incompletely understood. Here we show that NANOG partners with TBX3 and the PRC2 complex to maintain embryonic stem cell (ESC) identity by silencing PrE genes through newly identified distal enhancers. Loss of Nanog reduces PRC2-mediated repression of Gata6, initiating its expression independently of TBX3. Subsequent TBX3 upregulation enables its association with GATA6, driving a feed-forward programme that activates Gata6, Gata4 and Sox17 and promotes PrE differentiation. Thus, NANOG suppresses PrE fate not only by direct repression but also by preventing TBX3 from switching partners. These findings define a Nanog–Tbx3–Gata6 regulatory axis that integrates enhancer control, chromatin regulation and transcription factor redeployment to couple ESC maintenance with lineage commitment.
| Item ID: | 91586 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1469-3178 |
| Keywords: | Embryonic Stem Cells, Nanog, PRC2 Complex, Primitive Endoderm |
| Copyright Information: | © The Author(s).This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible. |
| Date Deposited: | 31 Jul 2026 04:30 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321101 Cancer cell biology @ 100% |
| SEO Codes: | 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100% |
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