KDM4 Demethylases: Structure, Function, and Inhibitors

KDM4 histone demethylases mainly catalyze the removal of methyl marks from H3K9 and H3K36 to epigenetically regulate chromatin structure and gene expression. KDM4 expression is strictly regulated to ensure proper function in a myriad of biological processes, including transcription, cellular proliferation and differentiation, DNA damage repair, immune response, and stem cell self-renewal. Aberrant expression of KDM4 demethylase has been documented in many types of blood and solid tumors, and thus, KDM4s represent promising therapeutic targets. In this chapter, we summarize the current knowledge of the structures and regulatory mechanisms of KDM4 proteins and our understanding of their alterations in human pathological processes with a focus on development and cancer. We also review the reported KDM4 inhibitors and discuss their potential as therapeutic agents.