Lysine-specific demethylase 4D (KDM4D)

Lysine-specific demethylase 4D (KDM4D) is an epigenetic enzyme belonging to the KDM4 family, specifically characterized by a Jumonji C (JmjC) domain. It catalyzes the removal (demethylation) of di- and trimethyl groups from lysine 9 (H3K9me2/me3) on histone H3, playing important roles in chromatin remodeling and transcriptional regulation[3][4]. Unlike other KDM4 family members, KDM4D features only the JmjN and JmjC domains, lacking the PHD and Tudor domains typically found in KDM4A-C[3][4]. KDM4D is implicated in several cellular processes, including the DNA damage response/repair, differentiation (notably adipogenesis), and hepatic stellate cell activation[1][2][3]. Overexpression or dysregulation of KDM4D has been observed in tumorigenesis and liver fibrosis, suggesting it is a potential therapeutic target in cancer and fibrotic diseases[2][3]. The molecular mechanism involves the removal of repressive histone marks, facilitating gene activation or DNA repair machinery recruitment. Currently, pan-inhibitors of the KDM4 family, such as 8-hydroxyquinoline, target KDM4D's demethylase activity, but selective KDM4D inhibitors and clinical biomarker strategies are still under research[3][5].

Other names

JMJD2DJHDM3DFLJ10251JmjC domain-containing histone demethylation protein 3DJumonji domain-containing protein 2D[histone H3]-trimethyl-L-lysine(9) demethylase 4DjmjC domain-containing histone demethylation protein 3Djumonji domain containing 2Dlysine (K)-specific demethylase 4D

Inhibition of H3K9 demethylation (blocking removal of di- and trimethyl marks on lysine 9 of histone H3); Modulation of DNA damage repair pathways (via epigenetic mechanisms)