Multi-omics elucidation of KDM5C, KDM6A, and KMT2B roles in cancer epigenetic dysregulation and transcriptional reprogramming.

ABSTRACT: Histone-modifying enzymes (HMEs) are critical regulators of tumorigenesis through epigenetic reprogramming. While mutations in HMEs are recognized drivers of cancer epigenome dysregulation, systematic comparative analyses of their mutational impacts and functional divergence across malignancies remain underexplored. Here, we investigated three HMEs frequently mutated in diverse cancers: KMT2B (H3K4me3 methyltransferase), KDM5C (H3K4me3 demethylase), and KDM6A (H3K27me3 demethylase). Using CRISPR/Cas9-engineered HEK293T knockout cell lines, we performed integrated multi-omics profiling that combined genome-wide chromatin accessibility, transcriptomics, and chromatin-bound proteomics. Contrary to expectations that KMT2B loss (H3K4me3 depletion) and KDM5C loss (H3K4me3 accumulation) would ind

SUBMITTER: Li T 

PROVIDER: S-EPMC12783180 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature