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Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance

In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen–induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that...

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Autores principales: Rivera-Gonzalez, Guillermo C., Droop, Alastair P., Rippon, Helen J., Tiemann, Katrin, Pellacani, Davide, Georgopoulos, Lindsay J., Maitland, Norman J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367184/
https://www.ncbi.nlm.nih.gov/pubmed/22362749
http://dx.doi.org/10.1093/nar/gks143
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author Rivera-Gonzalez, Guillermo C.
Droop, Alastair P.
Rippon, Helen J.
Tiemann, Katrin
Pellacani, Davide
Georgopoulos, Lindsay J.
Maitland, Norman J.
author_facet Rivera-Gonzalez, Guillermo C.
Droop, Alastair P.
Rippon, Helen J.
Tiemann, Katrin
Pellacani, Davide
Georgopoulos, Lindsay J.
Maitland, Norman J.
author_sort Rivera-Gonzalez, Guillermo C.
collection PubMed
description In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen–induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that the regulation of the hTGP gene depends mainly on retinoic acid (RA). We provide evidence that the retinoic acid receptor gamma (RAR-G) plays a major role in the regulation of the hTGP gene and that presence of the AR, but not its transcriptional transactivation activity, is critical for hTGP transcription. RA and androgen responsive elements (RARE and ARE) were mapped to the hTGP promoter by chromatin immunoprecipitation (ChIP), which also indicated that the active ARE and RARE sites were adjacent, suggesting that the antagonistic effect of androgen and RA is related to the relative position of binding sites. Publicly available AR and RAR ChIP-seq data was used to find gene potentially regulated by AR and RAR. Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically regulated by androgens and RA confirming that this regulation is not particular of hTGP.
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spelling pubmed-33671842012-06-05 Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance Rivera-Gonzalez, Guillermo C. Droop, Alastair P. Rippon, Helen J. Tiemann, Katrin Pellacani, Davide Georgopoulos, Lindsay J. Maitland, Norman J. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen–induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that the regulation of the hTGP gene depends mainly on retinoic acid (RA). We provide evidence that the retinoic acid receptor gamma (RAR-G) plays a major role in the regulation of the hTGP gene and that presence of the AR, but not its transcriptional transactivation activity, is critical for hTGP transcription. RA and androgen responsive elements (RARE and ARE) were mapped to the hTGP promoter by chromatin immunoprecipitation (ChIP), which also indicated that the active ARE and RARE sites were adjacent, suggesting that the antagonistic effect of androgen and RA is related to the relative position of binding sites. Publicly available AR and RAR ChIP-seq data was used to find gene potentially regulated by AR and RAR. Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically regulated by androgens and RA confirming that this regulation is not particular of hTGP. Oxford University Press 2012-06 2012-02-22 /pmc/articles/PMC3367184/ /pubmed/22362749 http://dx.doi.org/10.1093/nar/gks143 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), 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
Rivera-Gonzalez, Guillermo C.
Droop, Alastair P.
Rippon, Helen J.
Tiemann, Katrin
Pellacani, Davide
Georgopoulos, Lindsay J.
Maitland, Norman J.
Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title_full Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title_fullStr Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title_full_unstemmed Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title_short Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
title_sort retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367184/
https://www.ncbi.nlm.nih.gov/pubmed/22362749
http://dx.doi.org/10.1093/nar/gks143
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