Cargando…
The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes
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 br...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191390/ https://www.ncbi.nlm.nih.gov/pubmed/25223786 http://dx.doi.org/10.1093/nar/gku791 |
_version_ | 1782338652935815168 |
---|---|
author | Jangal, Maïka Couture, Jean-Philippe Bianco, Stéphanie Magnani, Luca Mohammed, Hisham Gévry, Nicolas |
author_facet | Jangal, Maïka Couture, Jean-Philippe Bianco, Stéphanie Magnani, Luca Mohammed, Hisham Gévry, Nicolas |
author_sort | Jangal, Maïka |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4191390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41913902015-04-02 The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes Jangal, Maïka Couture, Jean-Philippe Bianco, Stéphanie Magnani, Luca Mohammed, Hisham Gévry, Nicolas Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2014-10-13 2014-09-15 /pmc/articles/PMC4191390/ /pubmed/25223786 http://dx.doi.org/10.1093/nar/gku791 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene regulation, Chromatin and Epigenetics Jangal, Maïka Couture, Jean-Philippe Bianco, Stéphanie Magnani, Luca Mohammed, Hisham Gévry, Nicolas The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title | The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title_full | The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title_fullStr | The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title_full_unstemmed | The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title_short | The transcriptional co-repressor TLE3 suppresses basal signaling on a subset of estrogen receptor α target genes |
title_sort | transcriptional co-repressor tle3 suppresses basal signaling on a subset of estrogen receptor α target genes |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191390/ https://www.ncbi.nlm.nih.gov/pubmed/25223786 http://dx.doi.org/10.1093/nar/gku791 |
work_keys_str_mv | AT jangalmaika thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT couturejeanphilippe thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT biancostephanie thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT magnaniluca thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT mohammedhisham thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT gevrynicolas thetranscriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT jangalmaika transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT couturejeanphilippe transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT biancostephanie transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT magnaniluca transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT mohammedhisham transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes AT gevrynicolas transcriptionalcorepressortle3suppressesbasalsignalingonasubsetofestrogenreceptoratargetgenes |