The Pitx2c N‐terminal domain is a critical interaction domain required for asymmetric morphogenesis
The paired‐like homeodomain transcription factor Pitx2c has an essential role in patterning the left–right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N‐terminal domain of...
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| Veröffentlicht in: | Developmental dynamics 2009-10, Vol.238 (10), p.2459-2470 |
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| creator | Simard, Annie Di Giorgio, Luciano Amen, Melanie Westwood, Ashley Amendt, Brad A. Ryan, Aimee K. |
| description | The paired‐like homeodomain transcription factor Pitx2c has an essential role in patterning the left–right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N‐terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N‐terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N‐terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod‐1) promoter in transient transfection assays. A five amino acid region containing leucine‐41 is required for both of these effects. Our data suggest that the Pitx2c N‐terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left–right axis. Developmental Dynamics 238:2459–2470, 2009. © 2009 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/dvdy.22062 |
| format | Article |
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However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N‐terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N‐terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N‐terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod‐1) promoter in transient transfection assays. A five amino acid region containing leucine‐41 is required for both of these effects. Our data suggest that the Pitx2c N‐terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left–right axis. Developmental Dynamics 238:2459–2470, 2009. © 2009 Wiley‐Liss, Inc.</description><identifier>ISSN: 1058-8388</identifier><identifier>EISSN: 1097-0177</identifier><identifier>DOI: 10.1002/dvdy.22062</identifier><identifier>PMID: 19681163</identifier><language>eng</language><publisher>New York: Wiley‐Liss, Inc</publisher><subject>Amino Acid Sequence ; Animals ; Body Patterning - physiology ; Cells, Cultured ; Chick Embryo ; Gene Expression Regulation, Developmental ; Heart - anatomy & histology ; Heart - embryology ; heart looping ; Homeobox Protein PITX2 ; homeodomain ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; left–right patterning ; Leucine - metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Pitx2c ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics ; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - metabolism ; Promoter Regions, Genetic ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Sequence Alignment ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcriptional Activation</subject><ispartof>Developmental dynamics, 2009-10, Vol.238 (10), p.2459-2470</ispartof><rights>Copyright © 2009 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4852-5546f57b50a98d71247ac58b8a3e350b9ff066d6ce52a68f6e0959cff44b667f3</citedby><cites>FETCH-LOGICAL-c4852-5546f57b50a98d71247ac58b8a3e350b9ff066d6ce52a68f6e0959cff44b667f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdvdy.22062$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdvdy.22062$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19681163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Simard, Annie</creatorcontrib><creatorcontrib>Di Giorgio, Luciano</creatorcontrib><creatorcontrib>Amen, Melanie</creatorcontrib><creatorcontrib>Westwood, Ashley</creatorcontrib><creatorcontrib>Amendt, Brad A.</creatorcontrib><creatorcontrib>Ryan, Aimee K.</creatorcontrib><title>The Pitx2c N‐terminal domain is a critical interaction domain required for asymmetric morphogenesis</title><title>Developmental dynamics</title><addtitle>Dev Dyn</addtitle><description>The paired‐like homeodomain transcription factor Pitx2c has an essential role in patterning the left–right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N‐terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N‐terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N‐terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod‐1) promoter in transient transfection assays. A five amino acid region containing leucine‐41 is required for both of these effects. Our data suggest that the Pitx2c N‐terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left–right axis. Developmental Dynamics 238:2459–2470, 2009. © 2009 Wiley‐Liss, Inc.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Body Patterning - physiology</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Heart - anatomy & histology</subject><subject>Heart - embryology</subject><subject>heart looping</subject><subject>Homeobox Protein PITX2</subject><subject>homeodomain</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>left–right patterning</subject><subject>Leucine - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Pitx2c</subject><subject>Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics</subject><subject>Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Sequence Alignment</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcriptional Activation</subject><issn>1058-8388</issn><issn>1097-0177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtOwzAQhi0EoqWw4QDIa6QUO4kdZ4OEWl5SBSwAiZXlOHZrlMTFTgvZcQTOyElISXltWM1o5ptvpB-AfYyGGKHwKF_mzTAMEQ03QB-jNAkQTpLNVU9YwCLGemDH-0eEEKMx3gY9nFKGMY36QN3OFLwx9Uso4dX761utXGkqUcDclsJU0HgooHSmNrIdmqrdC1kbW30BTj0tjFM51NZB4ZuyVLUzEpbWzWd2qirljd8FW1oUXu2t6wDcnZ3eji6CyfX55ehkEsiYkTAgJKaaJBlBImV5gsM4EZKwjIlIRQRlqdaI0pxKRUJBmaYKpSSVWsdxRmmiowE47rzzRVaqXKqqdqLgc2dK4RpuheF_N5WZ8ald8gjhmKKoFRx2Aums907p71uM-Cpsvgqbf4bdwge_v_2g63RbAHfAsylU84-Kj-_HD530A-ayjh8</recordid><startdate>200910</startdate><enddate>200910</enddate><creator>Simard, Annie</creator><creator>Di Giorgio, Luciano</creator><creator>Amen, Melanie</creator><creator>Westwood, Ashley</creator><creator>Amendt, Brad A.</creator><creator>Ryan, Aimee K.</creator><general>Wiley‐Liss, Inc</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>5PM</scope></search><sort><creationdate>200910</creationdate><title>The Pitx2c N‐terminal domain is a critical interaction domain required for asymmetric morphogenesis</title><author>Simard, Annie ; Di Giorgio, Luciano ; Amen, Melanie ; Westwood, Ashley ; Amendt, Brad A. ; Ryan, Aimee K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4852-5546f57b50a98d71247ac58b8a3e350b9ff066d6ce52a68f6e0959cff44b667f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Body Patterning - physiology</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Heart - anatomy & histology</topic><topic>Heart - embryology</topic><topic>heart looping</topic><topic>Homeobox Protein PITX2</topic><topic>homeodomain</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>left–right patterning</topic><topic>Leucine - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Pitx2c</topic><topic>Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics</topic><topic>Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Sequence Alignment</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Simard, Annie</creatorcontrib><creatorcontrib>Di Giorgio, Luciano</creatorcontrib><creatorcontrib>Amen, Melanie</creatorcontrib><creatorcontrib>Westwood, Ashley</creatorcontrib><creatorcontrib>Amendt, Brad A.</creatorcontrib><creatorcontrib>Ryan, Aimee K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Simard, Annie</au><au>Di Giorgio, Luciano</au><au>Amen, Melanie</au><au>Westwood, Ashley</au><au>Amendt, Brad A.</au><au>Ryan, Aimee K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Pitx2c N‐terminal domain is a critical interaction domain required for asymmetric morphogenesis</atitle><jtitle>Developmental dynamics</jtitle><addtitle>Dev Dyn</addtitle><date>2009-10</date><risdate>2009</risdate><volume>238</volume><issue>10</issue><spage>2459</spage><epage>2470</epage><pages>2459-2470</pages><issn>1058-8388</issn><eissn>1097-0177</eissn><abstract>The paired‐like homeodomain transcription factor Pitx2c has an essential role in patterning the left–right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N‐terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N‐terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N‐terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod‐1) promoter in transient transfection assays. A five amino acid region containing leucine‐41 is required for both of these effects. Our data suggest that the Pitx2c N‐terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left–right axis. Developmental Dynamics 238:2459–2470, 2009. © 2009 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley‐Liss, Inc</pub><pmid>19681163</pmid><doi>10.1002/dvdy.22062</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Journals; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Body Patterning - physiology Cells, Cultured Chick Embryo Gene Expression Regulation, Developmental Heart - anatomy & histology Heart - embryology heart looping Homeobox Protein PITX2 homeodomain Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans left–right patterning Leucine - metabolism Molecular Sequence Data Mutagenesis, Site-Directed Pitx2c Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - metabolism Promoter Regions, Genetic Protein Isoforms - genetics Protein Isoforms - metabolism Sequence Alignment Transcription Factors - genetics Transcription Factors - metabolism Transcriptional Activation |
| title | The Pitx2c N‐terminal domain is a critical interaction domain required for asymmetric morphogenesis |
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