Histone lysine demethylase (KDM) subfamily 4: structures, functions and therapeutic potential

KDM4 histone demethylases catalyze the removal of methyl marks from histone lysine residues to epigenetically regulate chromatin structure and gene expression. KDM4 expression is tightly regulated to insure proper function in diverse biological processes, such as cellular differentiation. Mounting evidence has shown that disrupting KDM4 expression is implicated in the establishment and progression of multiple diseases including cancer. In particular, genomic regions encoding the KDM4A, B and C genes are often amplified, disrupting normal cellular proliferation. Furthermore, KDM4 demethylases are promising druggable targets. In this review, we highlight the latest advances in characterizing the structures and regulatory mechanisms of KDM4 proteins, as well as our current understanding of their alterations and roles in tumorigenesis. We also review the reported KDM4 inhibitors and discuss their potential as therapeutic agents.