Mutant p53 regulates enhancer-associated H3K4 monomethylation through interactions with the methyltransferase MLL4.

ABSTRACT: Monomethylation of histone H3 lysine 4 (H3K4me1) is enriched at enhancers that are primed for activation and the levels of this histone mark are frequently altered in various human cancers. Yet, how alterations in H3K4me1 are established and the consequences of these epigenetic changes in tumorigenesis are not well understood. Using ChIP-Seq in human colon cancer cells, we demonstrate that mutant p53 depletion results in decreased H3K4me1 levels at active enhancers that reveal a striking colocalization of mutant p53 and the H3K4 monomethyltransferase MLL4 following chronic tumor necrosis factor alpha (TNFα) signaling. We further reveal that mutant p53 forms physiological associations and direct interactions with MLL4 and promotes the enhancer binding of MLL4, which is required for TNFα-ind

SUBMITTER: Rahnamoun H 

PROVIDER: S-EPMC6109924 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature