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c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2025 Jan 24; Vol. 53 (3). - Publication Year :
- 2025
-
Abstract
- 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 inhibiting it with a JNK inhibitor can alleviate this suppression, promoting mesoderm cell differentiation. Consistently, knockdown of MBD3 enhances mesoderm generation, whereas MBD3 overexpression impedes it. Overexpressing c-JUN redirects differentiation toward a fibroblast-like lineage. Collectively, our findings suggest that c-JUN acts as a chromatin regulator to restrict the mesoderm cell fate.<br /> (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Humans
GATA4 Transcription Factor metabolism
GATA4 Transcription Factor genetics
DNA-Binding Proteins metabolism
DNA-Binding Proteins genetics
Mi-2 Nucleosome Remodeling and Deacetylase Complex metabolism
Mi-2 Nucleosome Remodeling and Deacetylase Complex genetics
Transcription Factors metabolism
Transcription Factors genetics
Cell Line
Gene Expression Regulation, Developmental
Cell Lineage genetics
Mesoderm cytology
Mesoderm metabolism
Cell Differentiation genetics
Chromatin metabolism
Pluripotent Stem Cells metabolism
Pluripotent Stem Cells cytology
Proto-Oncogene Proteins c-jun metabolism
Proto-Oncogene Proteins c-jun genetics
T-Box Domain Proteins genetics
T-Box Domain Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 53
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 39876710
- Full Text :
- https://doi.org/10.1093/nar/gkaf001