Jumonji C domain-containing histone demethylase (JmjC histone demethylase)

Jumonji C domain-containing histone demethylase refers to a **large family of Fe(II)- and 2-oxoglutarate-dependent enzymes that catalyze the demethylation of lysine or arginine residues on histone proteins**[1][3][4][6]. These enzymes play a central role in **epigenetic regulation by removing mono-, di-, or trimethyl marks from histone tails**, thereby modulating chromatin structure and gene expression. The family encompasses multiple subgroups, including the well-studied KDM2–KDM7 lysine demethylases[3]. JmjC demethylases are functionally diverse, participating in cell differentiation, proliferation, stress responses, and DNA damage repair[1]. Dysfunction or mutation in specific JmjC demethylases contributes to human diseases such as cancer, neurodevelopmental disorders, intellectual disability, and infertility[2][3]. Small-molecule inhibitors targeting these enzymes are under preclinical and clinical investigation for cancer and other diseases[3]. JmjC demethylases are epigenetic writers/erasers essential for normal development and cellular homeostasis, and their inhibition requires careful titration to avoid adverse on-target effects[3][4].

Other names

Jumonji C domain proteinJmjC-domain histone demethylaseKDM (for lysine demethylase, e.g., KDM2–KDM7 subfamilies)Jumonji domain-containing histone demethylaseJmjC demethylase

Inhibition of lysine demethylation on histone tails; Modulation of chromatin state and transcriptional repression/activation; Disruption of protein interactions involved in epigenetic regulation