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SMYD2 methylates KDM5A restricting its demethylase activity on the genome (and driving proliferation)

GSE297612 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 7 samples Submitted 2026/05/27 Platform GPL30173
Summary
Members of the KDM5 family of Jumonji histone demethylases have been implicated in a variety of human diseases including multiple cancers. The regulation of KDM5 enzyme levels and activity, however, is poorly understood. Here we report that KDM5A is methylated by SMYD2 and that this methylation impacts histone demethylase activity. A mutant KDM5A that can no longer be methylated at K1063 exhibits unique genomic sites of action, demethylates H3K4me3 more robustly and at new loci, has unique transcriptional effects and distinct protein-protein interactions. As a result, a number of cell proliferation pathways are affected and cancer cell growth is blunted. This study illustrates the functional consequences of post-translational modifications of lysine residues in enzymes impacting genomic histone demethylation, gene expression and signaling.
Published in
KDM5A methylation modulates its genomic demethylase and transcriptional actions
Tran TA, Gopinathan G, Nuñez CG et al. · The Journal of biological chemistry 2026 · PMID 41962864 · doi:10.1016/j.jbc.2026.111436
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Also filed as BioProject PRJNA1265261 and SRA study SRP586414. Searching any of these in the dataset finder brings you back here.

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