JmjC Histone Demethylases: Beyond Histone Lysine Demethylation

Journal article

Jumonji C histone lysine demethylases (JmjC-KDMs) are key chromatin regulators best known for catalysing histone lysine demethylation. There is growing evidence that JmjC-KDMs have a broader catalytic scope. This review summarises recent advances on JmjC-KDM activities beyond histone lysine demethylation, including arginine demethylation and arginine hydroxylation. We discuss how emerging insights into sequence-reactivity and inter-domain relationships, combinatorial post-translational modifications (PTMs), and cellular context shape substrate selectivity and enzymatic outcomes. These findings highlight substantial mechanistic flexibility within the JmjC-KDM family and may help prompt reconsideration of how their biochemistry is connected to physiological roles. We discuss implications for JmjC-KDM inhibitor development and outline outstanding questions, guiding future research concerning their roles in epigenetic regulation.

Authors: Bonnici, J; Schofield, CJ; Kawamura, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Swiss Chemical Society
• Journal: CHIMIA
• Volume: 80
• Issue: 3
• Pages: 138-144
• Publication date: 2026-03-25
• DOI: 10.2533/chimia.2026.138
• EISSN: 2673-2424
• ISSN: 0009-4293
• Language: English
• Keywords: Lysine; Histone methyltransferase; Histone code; Chromatin; Epigenetics; Arginine; Histone; Context (archaeology)