The catalytic domains of all human <scp>KDM5 JmjC</scp> demethylases catalyse <i>N</i>‐methyl arginine demethylation
Joanna Bonnici, Razanne Oueini, E. Salah, C. Johansson, Christopher J. Schofield, Akane Kawamura
Abstract
The demethylation of N ε ‐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 N ω ‐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 N ε ‐methyllysine demethylation. Although our study is limited to peptide fragments, the results should help guide biological studies investigating JmjC functions.