The catalytic domains of all human KDM5 JmjC demethylases catalyse N‐methyl arginine demethylation

Abstract

The demethylation of Nε‐methyllysine residues on histones by Jumonji‐C lysine demethylases (JmjC‐KDMs) has been established. A subset of JmjC‐KDMs has also been reported to have Nω‐methylarginine residue demethylase (RDM) activity. Here, we describe biochemical screening studies, showing that the catalytic domains of all human KDM5s (KDM5A‐KDM5D), KDM4E and, to a lesser extent, KDM4A/D, have both KDM and RDM activities with histone peptides. Ras GTPase‐activating protein‐binding protein 1 peptides were shown to be RDM substrates for KDM5C/D. No RDM activity was observed with KDM1A and the other JmjC‐KDMs tested. The results highlight the potential of JmjC‐KDMs to catalyse reactions other than Nε‐methyllysine demethylation. Although our study is limited to peptide fragments, the results should help guide biological studies investigating JmjC functions.