Imperial College London
Alternate

ProfessorLucaMagnani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Principal Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jangal:2014:nar/gku791,
author = {Jangal, M and Couture, J-P and Bianco, S and Magnani, L and Mohammed, H and Gevry, N},
doi = {nar/gku791},
journal = {Nucleic Acids Research},
pages = {11339--11348},
title = {The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor alpha target genes},
url = {http://dx.doi.org/10.1093/nar/gku791},
volume = {42},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Chromatin constitutes a repressive barrier to the process of ligand-dependent transcriptional activity of nuclear receptors. Nucleosomes prevent the binding of estrogen receptor α (ERα) in absence of ligand and thus represent an important level of transcriptional regulation. Here, we show that in breast cancer MCF-7 cells, TLE3, a co-repressor of the Groucho/Grg/TLE family, interacts with FoxA1 and is detected at regulatory elements of ERα target genes in absence of estrogen. As a result, the chromatin is maintained in a basal state of acetylation, thus preventing ligand-independent activation of transcription. In absence of TLE3, the basal expression of ERα target genes induced by E2 is increased. At the TFF1 gene, the recruitment of TLE3 to the chromatin is FoxA1-dependent and prevents ERα and RNA polymerase II recruitment to TFF1 gene regulatory elements. Moreover, the interaction of TLE3 with HDAC2 results in the maintenance of acetylation at a basal level. We also provide evidence that TLE3 is recruited at several other regulatory elements of ERα target genes and is probably an important co-regulator of the E2 signaling pathway. In sum, our results describe a mechanism by which TLE3 affects ligand dependency in ERα-regulated gene expression via its binding restricting function and its role in gene regulation by histone acetylation.
AU  - Jangal,M
AU  - Couture,J-P
AU  - Bianco,S
AU  - Magnani,L
AU  - Mohammed,H
AU  - Gevry,N
DO  - nar/gku791
EP  - 11348
PY  - 2014///
SN  - 1362-4962
SP  - 11339
TI  - The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor alpha target genes
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gku791
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347687100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/43014
VL  - 42
ER  -
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