Toggle Main Menu Toggle Search

Open Access padlockePrints

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 Gaughan, Professor Craig Robson, Dr Olivier Binda

Downloads


Licence

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


Abstract

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

URL: http://dx.doi.org/10.4161/epi.28864

DOI: 10.4161/epi.28864

PubMed id: PMC4143409


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share