Furthermore, developmental competence was diminished, correlating with impaired exit from pluripotency. MCM2-2A mutation challenged dynamic transitions in cellular states across the cell cycle, enhancing naïve pluripotency and reducing lineage priming in G1. Moreover, H3K9me3 loss at repeats caused derepression and H3K27me3 redistribution across bivalent promoters correlated with misexpression of developmental genes. This included widespread spurious deposition of repressive modifications, suggesting elevated epigenetic noise. Asymmetric segregation of parental histones H3-H4 in MCM2-2A mutants compromised mitotic inheritance of histone modifications and globally altered the epigenome. Here we show that transmission of histone-based information during DNA replication maintains epigenome fidelity and embryonic stem cell plasticity. How this may sustain the epigenome and cell identity remains unknown. Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. Visit Broad Come see what Broad is all about.Student opportunities Learn about Broad Institute's mentored research offerings for high school students, college students, and recent college graduates.Public programs Discover remarkable stories of scientific progress, and explore the intersections of science, medicine, and society.Learning resources Access free classroom materials and more for STEM educators, parents, students, tutors, and others.Broad Discovery Center Visit our free public educational space that showcases how researchers at the Broad and their colleagues around the world seek to understand and treat human disease.Art and science connection Explore the connection between art and science and how we bring together artists and Broad scientists through our artist-in-residence program, gallery exhibitions, and ongoing public conversations.Stanley Center for Psychiatric Research The Stanley Center aims to reduce the burden of serious mental illness by contributing new insights into pathogenesis, identifying biomarkers, and paving the way toward new treatments.Eric and Wendy Schmidt Center The EWSC is catalyzing a new field of interdisciplinary research at the intersection of data science and life science, aimed at improving human health. Novo Nordisk Foundation Center for Genomic Mechanisms of Disease This center is developing new paradigms and technologies to scale the discovery of biological mechanisms of common, complex diseases, by facilitating close collaborations between the Broad Institute and the Danish research community.Merkin Institute for Transformative Technologies in Healthcare The Merkin Institute is supporting early-stage ideas aimed at advancing powerful technological approaches for improving how we understand and treat disease.
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