The Roles of Jumonji-Type Oxygenases in Human Disease

Abstract

The iron- and 2-oxoglutarate-dependent oxygenases constitute a phylogenetically conserved class of enzymes that catalyze hydroxylation reactions in humans by acting on various types of substrates, including metabolic intermediates, amino acid residues in different proteins and various types of nucleic acids. The discovery of jumonji (Jmj), the founding member of a class of Jmj-type chromatin modifying enzymes and transcriptional regulators, has culminated in the discovery of several branches of histone lysine demethylases, with essential functions in regulating the epigenetic landscape of the chromatin environment. This work has now been considerably expanded into other aspects of epigenetic biology and includes the discovery of enzymatic steps required for methyl-cytosine demethylation as well as modification of RNA and ribosomal proteins. This overview aims to summarize the current knowledge on the human Jmj-type enzymes and their involvement in human pathological processes, including development, cancer, inflammation and metabolic diseases.

Keywords::

• chromatin modification
• epigenetic
• histone demethylation
• Jumonji
• lysine methylation
• oxygenases

Acknowledgements

The authors are grateful to Michael McDonough and Chris Schofield (Department of Chemistry, Oxford, UK) and Susanne Muller-Knapp (SGC Oxford, UK) for fruitful discussions and collaborations.

Financial & competing interests disclosure

Research in the authors’ laboratories is funded by the Oxford NIHR BRU, the Rosetrees Foundation, Bayer Healthcare, MRC, BBSRC, ARUK and GlaxoSmithKline. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from Abbvie, Boehringer Ingelheim, the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Eli Lilly and Company, Genome Canada, GlaxoSmithKline, the Ontario Ministry of Economic Development and Innovation, Janssen, the Novartis Research Foundation, Pfizer, Takeda and the Wellcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research in the authors’ laboratories is funded by the Oxford NIHR BRU, the Rosetrees Foundation, Bayer Healthcare, MRC, BBSRC, ARUK and GlaxoSmithKline. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from Abbvie, Boehringer Ingelheim, the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Eli Lilly and Company, Genome Canada, GlaxoSmithKline, the Ontario Ministry of Economic Development and Innovation, Janssen, the Novartis Research Foundation, Pfizer, Takeda and the Wellcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.