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SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

Lookup NU author(s): Daniel O'Neill, Dr Stuart Williamson, Dhuha Alkharaif, Dr Luke GaughanORCiD, Professor Craig Robson, Dr Olivier Binda



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signalling. Specifically, SETD6 associates with the estrogen receptor alpha (ERĪ±), histone deacetylase HDAC1, metastasis protein MTA2, and the transcriptional coactivator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC1 and MTA2. However, SETD6 behaves as a coactivator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signalling and cellular proliferation.

Publication metadata

Author(s): O'Neill DJ, Williamson SC, Alkharaif D, Monteiro ICM, Goudreault M, Gaughan L, Robson CN, Gingras AC, Binda O

Publication type: Article

Publication status: Published

Journal: Epigenetics

Year: 2014

Volume: 9

Issue: 7

Pages: 942-950

Print publication date: 01/07/2014

Online publication date: 21/04/2014

Acceptance date: 11/04/2014

Date deposited: 02/07/2015

ISSN (print): 1559-2294

ISSN (electronic): 1559-2308

Publisher: Landes Bioscience


DOI: 10.4161/epi.28864

PubMed id: PMC4143409


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Funder referenceFunder name
Newcastle's Biomedical Fellowship Programme
Wellcome Trust's Institutional Strategic Support Fund
2013MaySP005Breast Cancer Campaign charity
MOP-123322Canadian Institutes of Health Research
097823/Z/11/AWellcome Trust (closed comp)