Coactivator recruitment is enhanced by thyroid hormone receptor trimers
Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of na...
Gespeichert in:
| Veröffentlicht in: | Molecular and cellular endocrinology 2008-01, Vol.280 (1), p.47-62 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 62 |
|---|---|
| container_issue | 1 |
| container_start_page | 47 |
| container_title | Molecular and cellular endocrinology |
| container_volume | 280 |
| creator | Mengeling, Brenda J. Lee, Sangho Privalsky, Martin L. |
| description | Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRβ0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRβ0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRβ0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRβ0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRβ0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers. |
| doi_str_mv | 10.1016/j.mce.2007.09.011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2197157</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0303720707003668</els_id><sourcerecordid>70096607</sourcerecordid><originalsourceid>FETCH-LOGICAL-c449t-e5c6060337b2867bb6b655da7307a9ec213ee4b0aae8751d9012007282fc73a13</originalsourceid><addsrcrecordid>eNp9kE9LwzAchoMobk4_gBfpyVvrL2mbtAiCDP_BwIueQ5r-5jLWZibZYN_elA3_XDzlkOd98-Yh5JJCRoHym2XWacwYgMigzoDSIzKmlWBpBaU4JmPIIU8FAzEiZ94vIYIlq07JiFYAnBbFmDxNrdLBbFWwLnGo3caEDvuQGJ9gv1C9xjZpdklY7Jw1bbKwrrM9Diiuh0xwpkPnz8nJXK08XhzOCXl_fHibPqez16eX6f0s1UVRhxRLzYFDnouGVVw0DW94WbZK5CBUjZrRHLFoQCmsREnbGujwPVaxuRa5ovmE3O1715umw1bHqU6t5DquUG4nrTLy701vFvLDbiWjtaCliAXXhwJnPzfog-yM17haqR7txksBUHMOA0j3oHbWe4fz70coyEG_XMqoXw77JNQy6o-Zq9_rfhIH3xG43QMYHW0NOum1wUGyiUaDbK35p_4Lbn6W_g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70096607</pqid></control><display><type>article</type><title>Coactivator recruitment is enhanced by thyroid hormone receptor trimers</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Mengeling, Brenda J. ; Lee, Sangho ; Privalsky, Martin L.</creator><creatorcontrib>Mengeling, Brenda J. ; Lee, Sangho ; Privalsky, Martin L.</creatorcontrib><description>Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRβ0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRβ0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRβ0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRβ0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRβ0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2007.09.011</identifier><identifier>PMID: 18006144</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Cell Line ; Cercopithecus aethiops ; Chickens ; Coactivator ; Coregualtor recruitment ; Dimerization ; DNA - metabolism ; Histone Acetyltransferases - metabolism ; Mediator Complex Subunit 1 ; Nuclear Receptor Coactivator 1 ; Nuclear Receptor Coactivator 2 - metabolism ; Nuclear Receptor Coactivator 3 ; Organic Chemicals - pharmacology ; Response Elements ; Retinoid X Receptor alpha - agonists ; Retinoid X Receptor alpha - metabolism ; Thyroid hormone receptor ; Thyroid Hormone Receptors beta - drug effects ; Thyroid Hormone Receptors beta - genetics ; Thyroid Hormone Receptors beta - metabolism ; Trans-Activators - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic ; Transcriptional Activation ; Transfection ; Triiodothyronine - metabolism</subject><ispartof>Molecular and cellular endocrinology, 2008-01, Vol.280 (1), p.47-62</ispartof><rights>2007 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-e5c6060337b2867bb6b655da7307a9ec213ee4b0aae8751d9012007282fc73a13</citedby><cites>FETCH-LOGICAL-c449t-e5c6060337b2867bb6b655da7307a9ec213ee4b0aae8751d9012007282fc73a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0303720707003668$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18006144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mengeling, Brenda J.</creatorcontrib><creatorcontrib>Lee, Sangho</creatorcontrib><creatorcontrib>Privalsky, Martin L.</creatorcontrib><title>Coactivator recruitment is enhanced by thyroid hormone receptor trimers</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRβ0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRβ0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRβ0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRβ0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRβ0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers.</description><subject>Animals</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>Chickens</subject><subject>Coactivator</subject><subject>Coregualtor recruitment</subject><subject>Dimerization</subject><subject>DNA - metabolism</subject><subject>Histone Acetyltransferases - metabolism</subject><subject>Mediator Complex Subunit 1</subject><subject>Nuclear Receptor Coactivator 1</subject><subject>Nuclear Receptor Coactivator 2 - metabolism</subject><subject>Nuclear Receptor Coactivator 3</subject><subject>Organic Chemicals - pharmacology</subject><subject>Response Elements</subject><subject>Retinoid X Receptor alpha - agonists</subject><subject>Retinoid X Receptor alpha - metabolism</subject><subject>Thyroid hormone receptor</subject><subject>Thyroid Hormone Receptors beta - drug effects</subject><subject>Thyroid Hormone Receptors beta - genetics</subject><subject>Thyroid Hormone Receptors beta - metabolism</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><subject>Triiodothyronine - metabolism</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9LwzAchoMobk4_gBfpyVvrL2mbtAiCDP_BwIueQ5r-5jLWZibZYN_elA3_XDzlkOd98-Yh5JJCRoHym2XWacwYgMigzoDSIzKmlWBpBaU4JmPIIU8FAzEiZ94vIYIlq07JiFYAnBbFmDxNrdLBbFWwLnGo3caEDvuQGJ9gv1C9xjZpdklY7Jw1bbKwrrM9Diiuh0xwpkPnz8nJXK08XhzOCXl_fHibPqez16eX6f0s1UVRhxRLzYFDnouGVVw0DW94WbZK5CBUjZrRHLFoQCmsREnbGujwPVaxuRa5ovmE3O1715umw1bHqU6t5DquUG4nrTLy701vFvLDbiWjtaCliAXXhwJnPzfog-yM17haqR7txksBUHMOA0j3oHbWe4fz70coyEG_XMqoXw77JNQy6o-Zq9_rfhIH3xG43QMYHW0NOum1wUGyiUaDbK35p_4Lbn6W_g</recordid><startdate>20080102</startdate><enddate>20080102</enddate><creator>Mengeling, Brenda J.</creator><creator>Lee, Sangho</creator><creator>Privalsky, Martin L.</creator><general>Elsevier Ireland Ltd</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080102</creationdate><title>Coactivator recruitment is enhanced by thyroid hormone receptor trimers</title><author>Mengeling, Brenda J. ; Lee, Sangho ; Privalsky, Martin L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-e5c6060337b2867bb6b655da7307a9ec213ee4b0aae8751d9012007282fc73a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cell Line</topic><topic>Cercopithecus aethiops</topic><topic>Chickens</topic><topic>Coactivator</topic><topic>Coregualtor recruitment</topic><topic>Dimerization</topic><topic>DNA - metabolism</topic><topic>Histone Acetyltransferases - metabolism</topic><topic>Mediator Complex Subunit 1</topic><topic>Nuclear Receptor Coactivator 1</topic><topic>Nuclear Receptor Coactivator 2 - metabolism</topic><topic>Nuclear Receptor Coactivator 3</topic><topic>Organic Chemicals - pharmacology</topic><topic>Response Elements</topic><topic>Retinoid X Receptor alpha - agonists</topic><topic>Retinoid X Receptor alpha - metabolism</topic><topic>Thyroid hormone receptor</topic><topic>Thyroid Hormone Receptors beta - drug effects</topic><topic>Thyroid Hormone Receptors beta - genetics</topic><topic>Thyroid Hormone Receptors beta - metabolism</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><topic>Triiodothyronine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mengeling, Brenda J.</creatorcontrib><creatorcontrib>Lee, Sangho</creatorcontrib><creatorcontrib>Privalsky, Martin L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mengeling, Brenda J.</au><au>Lee, Sangho</au><au>Privalsky, Martin L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coactivator recruitment is enhanced by thyroid hormone receptor trimers</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2008-01-02</date><risdate>2008</risdate><volume>280</volume><issue>1</issue><spage>47</spage><epage>62</epage><pages>47-62</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRβ0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRβ0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRβ0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRβ0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRβ0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18006144</pmid><doi>10.1016/j.mce.2007.09.011</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0303-7207 |
| ispartof | Molecular and cellular endocrinology, 2008-01, Vol.280 (1), p.47-62 |
| issn | 0303-7207 1872-8057 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2197157 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Cell Line Cercopithecus aethiops Chickens Coactivator Coregualtor recruitment Dimerization DNA - metabolism Histone Acetyltransferases - metabolism Mediator Complex Subunit 1 Nuclear Receptor Coactivator 1 Nuclear Receptor Coactivator 2 - metabolism Nuclear Receptor Coactivator 3 Organic Chemicals - pharmacology Response Elements Retinoid X Receptor alpha - agonists Retinoid X Receptor alpha - metabolism Thyroid hormone receptor Thyroid Hormone Receptors beta - drug effects Thyroid Hormone Receptors beta - genetics Thyroid Hormone Receptors beta - metabolism Trans-Activators - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic Transcriptional Activation Transfection Triiodothyronine - metabolism |
| title | Coactivator recruitment is enhanced by thyroid hormone receptor trimers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T12%3A04%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Coactivator%20recruitment%20is%20enhanced%20by%20thyroid%20hormone%20receptor%20trimers&rft.jtitle=Molecular%20and%20cellular%20endocrinology&rft.au=Mengeling,%20Brenda%20J.&rft.date=2008-01-02&rft.volume=280&rft.issue=1&rft.spage=47&rft.epage=62&rft.pages=47-62&rft.issn=0303-7207&rft.eissn=1872-8057&rft_id=info:doi/10.1016/j.mce.2007.09.011&rft_dat=%3Cproquest_pubme%3E70096607%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70096607&rft_id=info:pmid/18006144&rft_els_id=S0303720707003668&rfr_iscdi=true |