TY - JOUR TI - An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability AU - Jain, Kanishk AU - Marunde, Matthew R AU - Burg, Jonathan M AU - Gloor, Susan L AU - Joseph, Faith M AU - Poncha, Karl F AU - Gillespie, Zachary B AU - Rodriguez, Keli L AU - Popova, Irina K AU - Hall, Nathan W AU - Vaidya, Anup AU - Howard, Sarah A AU - Taylor, Hailey F AU - Mukhsinova, Laylo AU - Onuoha, Ugochi C AU - Patteson, Emily F AU - Cooke, Spencer W AU - Taylor, Bethany C AU - Weinzapfel, Ellen N AU - Cheek, Marcus A AU - Meiners, Matthew J AU - Fox, Geoffrey C AU - Namitz, Kevin EW AU - Cowles, Martis W AU - Krajewski, Krzysztof AU - Sun, Zu-Wen AU - Cosgrove, Michael S AU - Young, Nicolas L AU - Keogh, Michael-Christopher AU - Strahl, Brian D A2 - Shi, Xiaobing A2 - Rathmell, W Kimryn VL - 12 PY - 2023 DA - 2023/05/19 SP - e82596 C1 - eLife 2023;12:e82596 DO - 10.7554/eLife.82596 UR - https://doi.org/10.7554/eLife.82596 AB - In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation. KW - chromatin KW - H3K4 methylation KW - readers KW - histone tail acetylation KW - nucleosomes KW - writers JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -