2022
DOI: 10.1101/2022.10.24.513607
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Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation during ESC differentiation

Abstract: Enhancers are essential in defining cell fates through the control of cell type specific gene expression. Enhancer activation is a multi-step process involving chromatin remodelers and histone modifiers including the monomethylation of H3K4 (H3K4me1) by MLL3 (KMT2C) and MLL4 (KMT2D). MLL3/4 are thought to be critical for enhancer activation and cognate gene expression including through the recruitment of acetyltransferases for H3K27. Here we test this model by evaluating the impact of MLL3/4 loss on chromatin … Show more

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Cited by 4 publications
(3 citation statements)
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“…Our data further imply that H3K27ac can persist when H3K4me1 is depleted, in agreement with a recent study reporting that H3K27ac is gained at hundreds of enhancers independently of MLL3/4 activity or H3K4me1 binding during ESC differentiation 72 . The requirement for enhancer priming, and the underlying mechanisms, are likely to be developmental context dependent.…”
Section: Potential Mechanisms Of Enhancer Priming By Cyclical Dna Met...supporting
confidence: 93%
“…Our data further imply that H3K27ac can persist when H3K4me1 is depleted, in agreement with a recent study reporting that H3K27ac is gained at hundreds of enhancers independently of MLL3/4 activity or H3K4me1 binding during ESC differentiation 72 . The requirement for enhancer priming, and the underlying mechanisms, are likely to be developmental context dependent.…”
Section: Potential Mechanisms Of Enhancer Priming By Cyclical Dna Met...supporting
confidence: 93%
“…For example, MLL3/4 proteins were shown to drive all dynamic enhancer H3K4me1 during the naïve to formative pluripotency transition and their loss changes cell morphology and slows proliferation. Yet, expression of nearby genes was little to not impacted 51 . This result strongly suggests additional molecular roles for MLL3/4 proteins.…”
Section: Discussionmentioning
confidence: 97%
“…recently investigated the differentiation behaviour of MLL3/4 DKO and MLL3 KO mESCs 38 . The KOs showed a strong delay in proliferation, however, loss of the chromatin modifiers had little effect on the overall exit from naive pluripotency, suggesting that extension of cell cycle length does not interfere with differentiation.…”
Section: Differentiation Delay Phenotypes Do Not Show Any Cell Cycle ...mentioning
confidence: 99%