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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http://dx.doi.org/10.1016/j.molcel.2022.01.027 | DOI Listing |
Cell Rep
December 2024
State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China; Tianjin Key Laboratory of Epigenetics for Organ Development of Premature Infants, Tianjin 300450, China. Electronic address:
Unintentional, early pregnancy alcohol consumption affects embryonic development. During the peri-implantation stage, coinciding with the transition from naive to primed pluripotency, the long isoform of KDM2B (KDM2BLF) underlies the de novo establishment of polycomb repressive complex (PRC) functions at promoters after fertilization. However, it remains unclear whether and how ethanol exposure affects this spatiotemporal chromatin setting.
View Article and Find Full Text PDFJ Adv Res
December 2024
State Key Laboratory of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China; Clinical Center for Heart Disease Research, School of Medicine, Tongji University, Shanghai 200120, China; Shanghai Arrhythmia Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China; Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China; Shanghai Frontiers Center of Nanocatalytic Medicine, Shanghai, 200092, China; Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai 200092, China; Department of Cell Biology, School of Medicine, Tongji University, Shanghai 200092, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China. Electronic address:
Introduction: Cell fate determination and transition are of paramount importance in biology and medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Upon activation, naive B cells exit their quiescent state and enter germinal center (GC) responses, a transition accompanied by increased protein synthesis. How protein translation efficiency is adequately adjusted to meet the increased demand requires further investigation. Here, we identify the methyltransferase METTL1 as a translational checkpoint during GC responses.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology (STAR) Research, University of Maryland School of Medicine, 685 W. Baltimore St. MSTF 5.34, Baltimore, MD, 21201, USA.
Domestic ferrets (Mustela putorius furo) are an emerging model species in biomedical research. While behavioral studies are a critical translational tool for evaluating neurologic function in disease models and toxicology studies, there is a lack of ferret-specific behavioral assays and corresponding data on baseline behavior. Play behavior is a promising target for evaluation of psychological well-being, particularly because ferrets engage in solitary and social play well into adulthood.
View Article and Find Full Text PDFNat Struct Mol Biol
October 2024
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
In mammals, 5-methylcytosine (5mC) and Polycomb repressive complex 2 (PRC2)-deposited histone 3 lysine 27 trimethylation (H3K27me3) are generally mutually exclusive at CpG-rich regions. As mouse embryonic stem cells exit the naive pluripotent state, there is massive gain of 5mC concomitantly with restriction of broad H3K27me3 to 5mC-free, CpG-rich regions. To formally assess how 5mC shapes the H3K27me3 landscape, we profiled the epigenome of naive and differentiated cells in the presence and absence of the DNA methylation machinery.
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