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

February 8, 2023

Title

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

Author

Joanna Bonnici, Razanne Oueini, Eidarus Salah, Catrine Johansson, Christopher J. Schofield, Akane Kawamura

Year

2023

Journal

FEBS Letters

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.

Instrument

LC-4000

Keywords

catalyst, KDM5, demethylation, KDM