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KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number96
JournalInternational Journal of Oncology
Issue number5
Early online date29 Oct 2021
Accepted/In press5 Aug 2021
E-pub ahead of print29 Oct 2021

Bibliographical note

Funding Information: The present study was funded by King's College London, CRUK KHP Centre Grant (grant no. C604/A25135) and the Blood Cancer UK (grant no. 20002). The authors also would like to extend their thanks to the Biotechnology and Biological Sciences Research (grant no. BB/T007737/1) and Medical Research Council (grant no. MR/T015845/1) for funding SJ postdoctoral research associate (PDRA) position within the laboratory of KMR. Publisher Copyright: © 2021 Spandidos Publications. All rights reserved.

King's Authors


Post-translational modification of histones serve a crucial role in the control of gene transcription. Trimethylation of lysine 4 on histone 3 is associated with transcription activation. There are currently six known methylases and six known demethylases that can control the methylation status of this site. Lysine demethylase 5B (KDM5B) is one such demethylase, which can repress gene expression. In particular KDM5B has been found to be overexpressed in a number of cancer types, and small-molecular weight inhibitors of its demethylase activity have been identified. Previous characterisation of Kdm5b knock-out mice has revealed that this genotype leads to either embryonic or neonatal lethality. However, the ΔA-T rich interaction domain (ΔARID)-KDM5B strain of mice, which have the ARID domain and five amino acids within the Jumonji (Jmj)N domain spliced out from KDM5B, remain viable and fertile. In the present study, ΔARID-KDM5B was found to have no demethylase activity as determined by in vitro demethylase assays and by immunofluorescence in transfected Cos-1 cells. Furthermore, molecular dynamic simulations revealed conformational changes within the ΔARID-KDM5B struc- ture compared with that in WT-KDM5B, particularly in the JmjC domain, which is responsible for the catalytic activity of WT-KDM5B. This supports the experimental data that shows the loss of demethylase activity. Since Kdm5b knock-out mice show varying degrees of lethality, these data suggest that KDM5B serves a crucial function in development in a manner that is independent of its demethylase activity.

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