TY - JOUR T1 - Nucleosomal Asymmetry Shapes Histone Mark Binding and Promotes Poising at Bivalent Domains JF - bioRxiv DO - 10.1101/2021.02.08.430127 SP - 2021.02.08.430127 AU - Elana Bryan AU - Marie Warburton AU - Kimberly M. Webb AU - Katy A. McLaughlin AU - Christos Spanos AU - Christina Ambrosi AU - Viktoria Major AU - Tuncay Baubec AU - Juri Rappsilber AU - Philipp Voigt Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/08/2021.02.08.430127.abstract N2 - Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one mark. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, despite presence of H3K4me3, thereby promoting a poised state. Strikingly, the bivalent mark combination further attracts chromatin proteins that are not recruited by each mark individually, including the histone acetyltransferase complex KAT6B (MORF). Knockout of KAT6B blocks neuronal differentiation, demonstrating that bivalency-specific readers are critical for proper ESC differentiation. These findings reveal how histone mark bivalency directly promotes establishment of a poised state at developmental genes, while highlighting how nucleosomal asymmetry is critical for histone mark readout and function.Competing Interest StatementThe authors have declared no competing interest. ER -