KDM4A
Description
The KDM4A (lysine demethylase 4A) is a protein-coding gene located on chromosome 1.
KDM4A is an enzyme encoded by the KDM4A gene in humans. It belongs to the Jumonji domain 2 (JMJD2) family and contains several domains, including a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. KDM4A is a nuclear protein that functions as a trimethylation-specific demethylase, converting specific trimethylated histone H3 lysine 9 and 36 residues to the dimethylated form and lysine 9 dimethylated residues to monomethyl. It also acts as a transcriptional repressor. Alterations in KDM4A have been linked to chromosomal instability leading to cancer. KDM4A is implicated as an oncogene in various cancers, including prostate, colon, and lung cancer, where it is overexpressed and promotes cell proliferation and tumor formation. In breast cancer cell lines, suppression of KDM4A reduces cancer cell proliferation, migration, and invasion. In mice, KDM4A is involved in processes leading to embryo implantation.
KDM4A is a histone demethylase that specifically removes methyl groups from lysine 9 and lysine 36 residues of histone H3. It plays a crucial role in regulating the histone code by modifying chromatin structure and influencing gene expression. KDM4A does not demethylate lysine 4, lysine 27 on histone H3, or lysine 20 on histone H4. It specifically targets trimethylated forms of lysine 9 and lysine 36 on histone H3, leaving mono- and dimethylated forms untouched. The demethylation process results in the production of formaldehyde and succinate. KDM4A participates in transcriptional repression by recruiting histone deacetylases and NCOR1 to repress ASCL2 and E2F-responsive promoters, respectively.
KDM4A is also known as JHDM3A, JMJD2, JMJD2A, TDRD14A.
