Available online 16 April 2024, 100978

JMJD3 is an H3K27me2/3 demethylase mediating transcriptional activation of associated genes.

JMJD3 is implicated in various physiological and pathological processes, including inflammation.

JMJD3 is a potential therapeutic target for multiple inflammatory diseases.

No JMJD3 inhibitor is clinically available up to now.

Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri-methylated groups from lysine 27 on histone 3 (H3K27me2/3). The erasure of these marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3’s role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

JMJD3

Inflammation

Histone demethylation

Inhibitor

© 2024 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.