Luke Gaughan
KDM4B is a master regulator of the estrogen receptor signalling cascade
Gaughan, Luke; Stockley, Jacqueline; Coffey, Kelly; O’Neill, Daniel; Jones, Dominic L.; Wade, Mark; Wright, Jamie; Moore, Madeleine; Tse, Sandy; Rogerson, Lynsey; Robson, Craig N.
Authors
Jacqueline Stockley
Kelly Coffey
Daniel O’Neill
Dominic L. Jones
Dr Mark Wade M.Wade@hull.ac.uk
Senior Lecturer in Molecular Genetics
Jamie Wright
Madeleine Moore
Sandy Tse
Lynsey Rogerson
Craig N. Robson
Abstract
The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment.
Citation
Gaughan, L., Stockley, J., Coffey, K., O’Neill, D., Jones, D. L., Wade, M., …Robson, C. N. (2013). KDM4B is a master regulator of the estrogen receptor signalling cascade. Nucleic Acids Research, 41(14), 6892-6904. https://doi.org/10.1093/nar/gkt469
Journal Article Type | Article |
---|---|
Acceptance Date | May 3, 2013 |
Online Publication Date | May 30, 2013 |
Publication Date | Aug 1, 2013 |
Deposit Date | Feb 4, 2019 |
Publicly Available Date | Mar 28, 2024 |
Journal | Nucleic Acids Research |
Print ISSN | 0305-1048 |
Electronic ISSN | 1362-4962 |
Publisher | Oxford University Press |
Peer Reviewed | Peer Reviewed |
Volume | 41 |
Issue | 14 |
Pages | 6892-6904 |
DOI | https://doi.org/10.1093/nar/gkt469 |
Public URL | https://hull-repository.worktribe.com/output/1271185 |
Publisher URL | https://academic.oup.com/nar/article/41/14/6892/1080007 |
Files
Article
(796 Kb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/3.0
Copyright Statement
ßThe Author(s) 2013. Published by Oxford University Press.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), whichpermits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Downloaded from https://academic.oup.com/nar/article-abstract/41/14/6892/1080007 by University of Hull user on 04 February 2019
You might also like
Downloadable Citations
About Repository@Hull
Administrator e-mail: repository@hull.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search