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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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| Published in: | Nucleic acids research 2012-06, Vol.40 (11), p.4825-4840 |
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| container_title | Nucleic acids research |
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| creator | Rivera-Gonzalez, Guillermo C Droop, Alastair P Rippon, Helen J Tiemann, Katrin Pellacani, Davide Georgopoulos, Lindsay J Maitland, Norman J |
| 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. |
| doi_str_mv | 10.1093/nar/gks143 |
| format | article |
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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.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gks143</identifier><identifier>PMID: 22362749</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Androgen receptors ; Androgens ; Androgens - pharmacology ; Cell Line, Tumor ; Chromatin ; Data processing ; Enhancer Elements, Genetic ; FIND gene ; Gene Expression Regulation, Enzymologic - drug effects ; Gene Regulation, Chromatin and Epigenetics ; Gene Regulatory Networks ; Humans ; Immunoprecipitation ; Male ; Metribolone - pharmacology ; Promoter Regions, Genetic ; Promoters ; Prostate ; Prostate - enzymology ; Prostate - metabolism ; Prostatic Neoplasms - enzymology ; Prostatic Neoplasms - genetics ; Protein-glutamine gamma -glutamyltransferase ; Receptors, Androgen - metabolism ; Receptors, Retinoic Acid - metabolism ; Receptors, Retinoic Acid - physiology ; Regulatory sequences ; Retinoic Acid Receptor gamma ; Retinoic acid receptors ; Transcription ; Transcriptional Activation ; Transglutaminases - genetics ; Transglutaminases - metabolism ; Tretinoin - pharmacology</subject><ispartof>Nucleic acids research, 2012-06, Vol.40 (11), p.4825-4840</ispartof><rights>The Author(s) 2012. 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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.</description><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Androgens - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Chromatin</subject><subject>Data processing</subject><subject>Enhancer Elements, Genetic</subject><subject>FIND gene</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Gene Regulation, Chromatin and Epigenetics</subject><subject>Gene Regulatory Networks</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Male</subject><subject>Metribolone - pharmacology</subject><subject>Promoter Regions, Genetic</subject><subject>Promoters</subject><subject>Prostate</subject><subject>Prostate - enzymology</subject><subject>Prostate - metabolism</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Protein-glutamine gamma -glutamyltransferase</subject><subject>Receptors, Androgen - metabolism</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Receptors, Retinoic Acid - physiology</subject><subject>Regulatory sequences</subject><subject>Retinoic Acid Receptor gamma</subject><subject>Retinoic acid receptors</subject><subject>Transcription</subject><subject>Transcriptional Activation</subject><subject>Transglutaminases - genetics</subject><subject>Transglutaminases - metabolism</subject><subject>Tretinoin - pharmacology</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNpVkd9qFTEQxkNR7Gn1pg8guRRh22STs3-8EErRVigI0l6H2exkT-xusibZ0_a9fEBzPG3Ri5DA_Ob7JvMRcsLZKWetOHMQzoa7yKU4ICsuqrKQbVW-Iism2LrgTDaH5CjGn4xxydfyDTksy0zVsl2R3z8wWeetpqBtT8H9PcEP6GhAjXPyIVLtp846pMlnbGNxm582xgVpnFFbk9u1dyn4kXpDN8sEjs7BxwQpl1IAF4dxSTBZBxEpPswBY7TefaJAnd_imM2GZYTs9kgdpnsf7ui9TRvaBQ89Bhrt4HZG4DS-Ja8NjBHfPd3H5Pbrl5uLq-L6--W3i_PrQkvOU5H7TFcZrs26Bc06RC1NKUqGpey5qYzga1PrrtN9DQZbKVjL-7y0Ghps2kock8973XnpJuw15i_CqOZgJwiPyoNV_1ec3ajBb5UQVc0bmQU-PAkE_2vBmNRko8ZxBId-iYqzsmG7ieqMftyjOu8tBjQvNpypXcwqx6z2MWf4_b-DvaDPuYo_Y3is5w</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Rivera-Gonzalez, Guillermo C</creator><creator>Droop, Alastair P</creator><creator>Rippon, Helen J</creator><creator>Tiemann, Katrin</creator><creator>Pellacani, Davide</creator><creator>Georgopoulos, Lindsay J</creator><creator>Maitland, Norman J</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120601</creationdate><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><author>Rivera-Gonzalez, Guillermo C ; Droop, Alastair P ; Rippon, Helen J ; Tiemann, Katrin ; Pellacani, Davide ; Georgopoulos, Lindsay J ; Maitland, Norman J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-adefb6f1cf59ac0beec4f2320e24d1f6f315f7cbbcd7afe943091d0307a8e8963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Androgens - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Chromatin</topic><topic>Data processing</topic><topic>Enhancer Elements, Genetic</topic><topic>FIND gene</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Gene Regulation, Chromatin and Epigenetics</topic><topic>Gene Regulatory Networks</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Male</topic><topic>Metribolone - pharmacology</topic><topic>Promoter Regions, Genetic</topic><topic>Promoters</topic><topic>Prostate</topic><topic>Prostate - enzymology</topic><topic>Prostate - metabolism</topic><topic>Prostatic Neoplasms - enzymology</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Protein-glutamine gamma -glutamyltransferase</topic><topic>Receptors, Androgen - metabolism</topic><topic>Receptors, Retinoic Acid - metabolism</topic><topic>Receptors, Retinoic Acid - physiology</topic><topic>Regulatory sequences</topic><topic>Retinoic Acid Receptor gamma</topic><topic>Retinoic acid receptors</topic><topic>Transcription</topic><topic>Transcriptional Activation</topic><topic>Transglutaminases - genetics</topic><topic>Transglutaminases - metabolism</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rivera-Gonzalez, Guillermo C</creatorcontrib><creatorcontrib>Droop, Alastair P</creatorcontrib><creatorcontrib>Rippon, Helen J</creatorcontrib><creatorcontrib>Tiemann, Katrin</creatorcontrib><creatorcontrib>Pellacani, Davide</creatorcontrib><creatorcontrib>Georgopoulos, Lindsay J</creatorcontrib><creatorcontrib>Maitland, Norman J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rivera-Gonzalez, Guillermo C</au><au>Droop, Alastair P</au><au>Rippon, Helen J</au><au>Tiemann, Katrin</au><au>Pellacani, Davide</au><au>Georgopoulos, Lindsay J</au><au>Maitland, Norman J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>40</volume><issue>11</issue><spage>4825</spage><epage>4840</epage><pages>4825-4840</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><abstract>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.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>22362749</pmid><doi>10.1093/nar/gks143</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nucleic acids research, 2012-06, Vol.40 (11), p.4825-4840 |
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| source | PubMed Central（OA）; OUP_牛津大学出版社现刊 |
| subjects | Androgen receptors Androgens Androgens - pharmacology Cell Line, Tumor Chromatin Data processing Enhancer Elements, Genetic FIND gene Gene Expression Regulation, Enzymologic - drug effects Gene Regulation, Chromatin and Epigenetics Gene Regulatory Networks Humans Immunoprecipitation Male Metribolone - pharmacology Promoter Regions, Genetic Promoters Prostate Prostate - enzymology Prostate - metabolism Prostatic Neoplasms - enzymology Prostatic Neoplasms - genetics Protein-glutamine gamma -glutamyltransferase Receptors, Androgen - metabolism Receptors, Retinoic Acid - metabolism Receptors, Retinoic Acid - physiology Regulatory sequences Retinoic Acid Receptor gamma Retinoic acid receptors Transcription Transcriptional Activation Transglutaminases - genetics Transglutaminases - metabolism Tretinoin - pharmacology |
| title | Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance |
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