biostudies-literatureZhang RGuangzhou Key Laboratory of Biological Targeting Diagnosis and TherapyKey Laboratory of Guangdong Higher Education InstitutesNational Natural Science Foundation of ChinaScience and Technology Development FundScience and Technology Projects in Guangzhougkaf001https://www.ebi.ac.uk/biostudies/studies/S-EPMC11760979biostudies-literatureUnknown53(3)Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency. Instead, it functions as a repressor to constrain mesoderm development while having a negligible impact on ectoderm differentiation. c-JUN interacts with MBD3-NuRD complex, which helps maintain chromatin in a low accessibility state at mesoderm-related genes during the differentiation of human pluripotent stem cells into mesoderm. Furthermore, c-JUN specifically inhibits the activation of key mesoderm factors, such as EOMES and GATA4. Knocking out c-JUN or inhibitingNucleic acids researchc-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.PMC117609792023A03J00450093/2024/AFJ2021KSYS009322705742022010203792023A04J015692068201Li GChen JLi DXiang DZhang XHutchins APQin DZhang RWang ZSu HZhang QPei Dfalsec-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency. Instead, it functions as a repressor to constrain mesoderm development while having a negligible impact on ectoderm differentiation. c-JUN interacts with MBD3-NuRD complex, which helps maintain chromatin in a low accessibility state at mesoderm-related genes during the differentiation of human pluripotent stem cells into mesoderm. Furthermore, c-JUN specifically inhibits the activation of key mesoderm factors, such as EOMES and GATA4. Knocking out c-JUN or inhibiting2025-01-01T00:00:00Z2025 Jan2026-06-02T20:37:25.517Z2025-04-03T23:57:17.033ZS-EPMC117609793987671010.1093/nar/gkaf001