Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.

ABSTRACT: Somatic heterozygous mutations in the active site of the enhancer of zeste homolog 2 (EZH2) are prevalent in diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). The methyltransferase activity of EZH2 towards lysine 27 on histone H3 (H3K27) and non-histone proteins is dysregulated by the presence of gain-of-function (GOF) and loss-of-function (LOF) mutations altering chromatin compaction, protein complex recruitment, and transcriptional regulation. In this study, a comprehensive multi-omics approach was carried out to characterize the effects of differential H3K27me3 deposition driven by EZH2 mutations. Three stable isogenic mutants (EZH2^Y641F, EZH2^A677G, and EZH2H^689A/F667I) were examined using EpiProfile, H3K27me3 CUT&Tag, ATAC-Seq, tra

SUBMITTER: Aldana J 

PROVIDER: S-EPMC10380343 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature