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Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription
Activity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I(–)) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879507/ https://www.ncbi.nlm.nih.gov/pubmed/20123735 http://dx.doi.org/10.1093/nar/gkq023 |
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author | Alotaibi, Hani Yaman, Elif Salvatore, Domenico Di Dato, Valeria Telkoparan, Pelin Di Lauro, Roberto Tazebay, Uygar H. |
author_facet | Alotaibi, Hani Yaman, Elif Salvatore, Domenico Di Dato, Valeria Telkoparan, Pelin Di Lauro, Roberto Tazebay, Uygar H. |
author_sort | Alotaibi, Hani |
collection | PubMed |
description | Activity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I(–)) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances NIS expression in a subset of breast cancer cell lines and in experimental breast cancer models. Indirect tRA stimulation of NIS in breast cancer cells is very well documented; however, direct upregulation by tRA-activated nuclear receptors has not been identified yet. Aiming to uncover cis-acting elements directly regulating NIS expression, we screened evolutionary-conserved non-coding genomic sequences for responsiveness to tRA in MCF-7. Here, we report that a potent enhancer in the first intron of NIS mediates direct regulation by tRA-stimulated nuclear receptors. In vitro as well as in vivo DNA–protein interaction assays revealed direct association between retinoic acid receptor-α (RARα) and retinoid-X-receptor (RXR) with this enhancer. Moreover, using chromatin immunoprecipitation (ChIP) we uncovered early events of NIS transcription in response to tRA, which require the interaction of several novel intronic tRA responsive elements. These findings indicate a complex interplay between nuclear receptors, RNA Pol-II and multiple intronic RAREs in NIS gene, and they establish a novel mechanistic model for tRA-induced gene transcription. |
format | Text |
id | pubmed-2879507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28795072010-06-02 Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription Alotaibi, Hani Yaman, Elif Salvatore, Domenico Di Dato, Valeria Telkoparan, Pelin Di Lauro, Roberto Tazebay, Uygar H. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Activity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I(–)) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances NIS expression in a subset of breast cancer cell lines and in experimental breast cancer models. Indirect tRA stimulation of NIS in breast cancer cells is very well documented; however, direct upregulation by tRA-activated nuclear receptors has not been identified yet. Aiming to uncover cis-acting elements directly regulating NIS expression, we screened evolutionary-conserved non-coding genomic sequences for responsiveness to tRA in MCF-7. Here, we report that a potent enhancer in the first intron of NIS mediates direct regulation by tRA-stimulated nuclear receptors. In vitro as well as in vivo DNA–protein interaction assays revealed direct association between retinoic acid receptor-α (RARα) and retinoid-X-receptor (RXR) with this enhancer. Moreover, using chromatin immunoprecipitation (ChIP) we uncovered early events of NIS transcription in response to tRA, which require the interaction of several novel intronic tRA responsive elements. These findings indicate a complex interplay between nuclear receptors, RNA Pol-II and multiple intronic RAREs in NIS gene, and they establish a novel mechanistic model for tRA-induced gene transcription. Oxford University Press 2010-06 2010-01-31 /pmc/articles/PMC2879507/ /pubmed/20123735 http://dx.doi.org/10.1093/nar/gkq023 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Alotaibi, Hani Yaman, Elif Salvatore, Domenico Di Dato, Valeria Telkoparan, Pelin Di Lauro, Roberto Tazebay, Uygar H. Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title | Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title_full | Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title_fullStr | Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title_full_unstemmed | Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title_short | Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription |
title_sort | intronic elements in the na+/i- symporter gene (nis) interact with retinoic acid receptors and mediate initiation of transcription |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879507/ https://www.ncbi.nlm.nih.gov/pubmed/20123735 http://dx.doi.org/10.1093/nar/gkq023 |
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