biostudies-literatureDupere-Richer DNCI NIH HHS1508-1520https://www.ebi.ac.uk/biostudies/studies/S-EPMC11952010biostudies-literatureUnknown144(14)<h4>Abstract</h4>The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA, which encode regulators of major histocompatibility complex genes. Patient data indicate that NLRC5 and CIITA are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A, and decreased gene expressionBloodKDM6A regulates immune response genes in multiple myeloma.PMC11952010R50 CA293837R01 CA269661Barwick BGLi JQuickstad GKulis MEzponda TMaji STonon GLicht JDDupere-Richer DRiva ASobh AZhang WMitsiades CSMartin-Subero JIDe UBennett RLCasellas Roman HPiper CBoise LHfalseKDM6A regulates immune response genes in multiple myeloma.<h4>Abstract</h4>The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA, which encode regulators of major histocompatibility complex genes. Patient data indicate that NLRC5 and CIITA are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A, and decreased gene expression2024-01-01T00:00:00Z2024 Oct2026-06-04T00:04:42.853Z2026-05-03T03:11:51.44ZS-EPMC119520103904677010.1182/blood.2024024518