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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.
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
URL: http://dx.doi.org/10.4161/epi.28864
DOI: 10.4161/epi.28864
PubMed id: PMC4143409
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