Lysine demethylase 4C (KDM4C)

Lysine demethylase 4C (KDM4C, JMJD2C) is a nuclear enzyme belonging to the Jumonji domain family, equipped with JmjN, JmjC, PHD, and Tudor domains, and catalyzes the removal of methyl groups from di- and tri-methylated lysine residues 9 and 36 on histone H3. This demethylation regulates transcription, chromatin structure, stem cell maintenance, and developmental processes, with highly context-dependent functions in healthy tissue and malignancies. JMJD2C serves as a co-activator for key transcription factors (e.g., HIF-1α), is essential for maintaining stem cell pluripotency, and is strongly implicated in cancer progression through its epigenetic modifications. Its overexpression is associated with tumor proliferation, metastasis, and poor outcomes in multiple cancer types, making it a promising therapeutic target for small molecule inhibitors and other regulatory agents. Selective targeting remains a challenge due to its roles in normal embryogenesis and stem cell biology.

Other names

KDM4CJMJD2CGASC1JHDM3CTDRD14C

Inhibition of histone demethylase activity (most small molecule inhibitors act by preventing JMJD2C from demethylating H3K9 and H3K36); Induction of apoptosis/cell cycle arrest (in cancer models; via depletion or inhibition of JMJD2C); Restoration of normal gene repression (by blocking H3K9 demethylation in cancer or stem cells).