Structure and function of dioxygenases in histone demethylation and DNA/RNA demethylation

Cheng Dong; Heng Zhang; Chao Xu; Cheryl H Arrowsmith; Jinrong Min

doi:10.1107/S2052252514020922

Structure and function of dioxygenases in histone demethylation and DNA/RNA demethylation

IUCrJ. 2014 Oct 28;1(Pt 6):540-9. doi: 10.1107/S2052252514020922. eCollection 2014 Nov 1.

Authors

Cheng Dong¹, Heng Zhang¹, Chao Xu¹, Cheryl H Arrowsmith², Jinrong Min³

Affiliations

¹ Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
² Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada ; Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
³ Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada ; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Abstract

Iron(II) and 2-oxoglutarate (2OG)-dependent dioxygenases involved in histone and DNA/RNA demethylation convert the cosubstrate 2OG and oxygen to succinate and carbon dioxide, resulting in hydroxylation of the methyl group of the substrates and subsequent demethylation. Recent evidence has shown that these 2OG dioxygenases play vital roles in a variety of biological processes, including transcriptional regulation and gene expression. In this review, the structure and function of these dioxygenases in histone and nucleic acid demethylation will be discussed. Given the important roles of these 2OG dioxygenases, detailed analysis and comparison of the 2OG dioxygenases will guide the design of target-specific small-molecule chemical probes and inhibitors.

Keywords: ALKBH5; DNA/RNA demethylation; N6-methyladenosine; dioxygenases; histone demethylation.

Publication types

Review

Grants and funding

092809/Wellcome Trust/United Kingdom