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

Abstract

The demethylation of N e -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 e -methyllysine demethylation. Although our study is limited to peptide fragments, the results should help guide biological studies investigating JmjC functions.

Domain architecture and protein–protein interactions regulate KDM5A recruitment to the chromatin

“…A recent in vitro study reported that KDM5 proteins are capable of arginine demethylation (RDM) on H3 and H4 peptides. It was shown that the catalytic domain of all four members of the KDM5 family, including KDM5A, is capable of demethylation of H3R2me2a residues on peptide substrate in vitro [ 44 ]. However, in vivo confirmation of KDM5A’s involvement on H3R2me2a is yet to be proven.…”