Lysine-specific demethylase 3 family (KDM3)

The KDM3 family consists of JmjC domain-containing histone demethylases, primarily KDM3A, KDM3B, and KDM3C, which specifically remove mono- and di-methyl marks from lysine 9 of histone H3 (H3K9me1/2). These enzymes act as transcriptional co-activators by relaxing chromatin structure, facilitating the binding of transcription factors like the androgen receptor (AR) and hypoxia-inducible factor 1-alpha (HIF-1alpha). KDM3 proteins play critical roles in diverse physiological processes, including spermatogenesis, sex determination, and energy metabolism. In pathology, their overexpression is frequently linked to the progression of various cancers, such as prostate, breast, and lung cancer, where they drive oncogenic gene expression programs. Consequently, the KDM3 family is a significant therapeutic target, with several small-molecule inhibitors like IOX1 and JIB-04 being explored in preclinical studies to modulate epigenetic states in disease.

Other names

JHDM2 familyJMJD1 familyJumonji domain-containing protein 1 familyH3K9me1/2 demethylase family

Inhibition of histone demethylase activity by competing with the 2-oxoglutarate cofactor or chelating the catalytic Fe(II) ion, leading to increased H3K9me1/2 levels and transcriptional silencing of target genes.