Journal
MOLECULAR CELL
Volume 82, Issue 6, Pages 1169-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2022.01.027
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Funding
- National Key Research and Development Program [2017YFA0504102]
- National Natural Science Foundation of China [81772676, 31970579, 32001025, 32030022]
- Natural Science Foundation of Tianjin Municipal Science and Tech-nology Commission [18JCJQJC48200]
- Key Research Project of Tian-jin Education Commission [2020ZD13]
- Chinese Academy of Medical Sciences [157-Z20-04]
- National Youth Talent Support Program
- Danish National Research Foundation [DNRF82]
- HHMI In-ternational Research Scholar grant [55008737]
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This study reveals the dynamic chromatin configuration of CGIs during exit from naive pluripotency and provides a conceptual framework for the spatiotemporal establishment of PcG functions.
Polycomb group (PcG) proteins are essential for post-implantation development by depositing repressive histone modifications at promoters, mainly CpG islands (CGIs), of developmental regulator genes. However, promoter PcG marks are erased after fertilization and de novo established in peri-implantation embryos, coinciding with the transition from naive to primed pluripotency. Nevertheless, the molecular basis for this establishment remains unknown. In this study, we show that the expression of the long KDM2B isoform (KDM2BLF), which contains the demethylase domain, is specifically induced at peri-implantation and that its H3K36me2 demethylase activity is required for PcG enrichment at CGIs. Moreover, KDM2BLF interacts with BRG1/BRM-associated factor (BAF) and stabilizes BAF occupancy at CGIs for subsequent gain of accessibility, which precedes PcG enrichment. Consistently, KDM2BLF inactivation results in significantly delayed post-implantation development. In summary, our data unveil dynamic chromatin configuration of CGIs during exit from naive pluripotency and provide a conceptual framework for the spatiotemporal establishment of PcG functions.
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