UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature

Abu-Hanna, Jeries; Patel, Jigisha A; Anastasakis, Evangelos; Cohen, Richard; Clapp, Lucie H; Loizidou, Marilena; Eddama, Mohammad MR; (2022) Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature. Clinical Epigenetics , 14 , Article 98. 10.1186/s13148-022-01305-8. Green open access

[thumbnail of s13148-022-01305-8.pdf]
Preview
Text
s13148-022-01305-8.pdf - Published Version

Download (2MB) | Preview

Abstract

Histone 3 lysine 27 (H3K27) demethylation constitutes an important epigenetic mechanism of gene activation. It is mediated by the Jumonji C domain-containing lysine demethylases KDM6A and KDM6B, both of which have been implicated in a wide myriad of diseases, including blood and solid tumours, autoimmune and inflammatory disorders, and infectious diseases. Here, we review and summarise the pre-clinical evidence, both in vitro and in vivo, in support of the therapeutic potential of inhibiting H3K27-targeting demethylases, with a focus on the small-molecule inhibitor GSK-J4. In malignancies, KDM6A/B inhibition possesses the ability to inhibit proliferation, induce apoptosis, promote differentiation, and heighten sensitivity to currently employed chemotherapeutics. KDM6A/B inhibition also comprises a potent anti-inflammatory approach in inflammatory and autoimmune disorders associated with inappropriately exuberant inflammatory and autoimmune responses, restoring immunological homeostasis to inflamed tissues. With respect to infectious diseases, KDM6A/B inhibition can suppress the growth of infectious pathogens and attenuate the immunopathology precipitated by these pathogens. The pre-clinical in vitro and in vivo data, summarised in this review, suggest that inhibiting H3K27 demethylases holds immense therapeutic potential in many diseases.

Type: Article
Title: Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13148-022-01305-8
Publisher version: https://doi.org/10.1186/s13148-022-01305-8
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords: Epigenetics, H3K27, Histone lysine demethylase, UTX, JMJD3, KDM6A, KDM6B, Cancer, Infammation, Autoimmune diseases, Infectious diseases, GSK-J4
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10153198
Downloads since deposit
25Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item