skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration
Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-11, Vol.107 (48), p.20750-20755 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Park, Chong Yon Pierce, Stephanie A. von Drehle, Morgan Ivey, Kathryn N. Morgan, Jayson A. Blau, Helen M. Srivastava, Deepak Olson, Eric N. |
| description | Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC -/- adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC -/- mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice. |
| doi_str_mv | 10.1073/pnas.1013493107 |
| format | Article |
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We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC -/- adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC -/- mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1013493107</identifier><identifier>PMID: 21071677</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adipocytes ; Animals ; Animals, Newborn ; Artificial satellites ; Biological Sciences ; Body Patterning ; Cardiac muscle ; Cardiomyocytes ; Cell growth ; Cell Proliferation ; Cell survival ; Chromatin ; Chromatin remodeling ; Deoxyribonucleic acid ; Development ; Developmental biology ; DNA ; DNA-binding protein ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Embryo, Mammalian - metabolism ; Embryo, Mammalian - pathology ; Embryos ; Gene deletion ; Gene expression regulation ; Gene Expression Regulation, Developmental ; Gene Targeting ; Heart ; Heart - growth & development ; Heart Ventricles - abnormalities ; Heart Ventricles - embryology ; Heart Ventricles - pathology ; histone methyltransferase ; Hypoplasia ; Injuries ; Lethality ; Mice ; Molecular Chaperones - metabolism ; Muscle Development - genetics ; Muscle Development - physiology ; Muscle Fibers, Skeletal - metabolism ; Muscle Fibers, Skeletal - pathology ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Muscle, Skeletal - embryology ; Muscle, Skeletal - growth & development ; Muscle, Skeletal - pathology ; Muscles ; Myocardium - metabolism ; Myocardium - pathology ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Organ Specificity - genetics ; Organogenesis - genetics ; Protein Binding ; Proteins ; Regeneration - physiology ; regulatory proteins ; Rodents ; satellite cells ; Skeletal muscle ; Skeletal muscle satellite cells ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-11, Vol.107 (48), p.20750-20755</ispartof><rights>Copyright National Academy of Sciences Nov 30, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-68eb6a3c8602f423cead976ab638bd5bee5d079c45c7fdd9793efe63777ee18c3</citedby><cites>FETCH-LOGICAL-c596t-68eb6a3c8602f423cead976ab638bd5bee5d079c45c7fdd9793efe63777ee18c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/48.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25756775$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25756775$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21071677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Chong Yon</creatorcontrib><creatorcontrib>Pierce, Stephanie A.</creatorcontrib><creatorcontrib>von Drehle, Morgan</creatorcontrib><creatorcontrib>Ivey, Kathryn N.</creatorcontrib><creatorcontrib>Morgan, Jayson A.</creatorcontrib><creatorcontrib>Blau, Helen M.</creatorcontrib><creatorcontrib>Srivastava, Deepak</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><title>skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC -/- adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC -/- mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.</description><subject>Adipocytes</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Artificial satellites</subject><subject>Biological Sciences</subject><subject>Body Patterning</subject><subject>Cardiac muscle</subject><subject>Cardiomyocytes</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Cell survival</subject><subject>Chromatin</subject><subject>Chromatin remodeling</subject><subject>Deoxyribonucleic acid</subject><subject>Development</subject><subject>Developmental biology</subject><subject>DNA</subject><subject>DNA-binding protein</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryo, Mammalian - pathology</subject><subject>Embryos</subject><subject>Gene deletion</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Targeting</subject><subject>Heart</subject><subject>Heart - growth & development</subject><subject>Heart Ventricles - abnormalities</subject><subject>Heart Ventricles - embryology</subject><subject>Heart Ventricles - pathology</subject><subject>histone methyltransferase</subject><subject>Hypoplasia</subject><subject>Injuries</subject><subject>Lethality</subject><subject>Mice</subject><subject>Molecular Chaperones - metabolism</subject><subject>Muscle Development - genetics</subject><subject>Muscle Development - physiology</subject><subject>Muscle Fibers, Skeletal - metabolism</subject><subject>Muscle Fibers, Skeletal - pathology</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Muscle, Skeletal - embryology</subject><subject>Muscle, Skeletal - growth & development</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscles</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Organ Specificity - genetics</subject><subject>Organogenesis - genetics</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Regeneration - physiology</subject><subject>regulatory proteins</subject><subject>Rodents</subject><subject>satellite cells</subject><subject>Skeletal muscle</subject><subject>Skeletal muscle satellite cells</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhiMEokvhzAlkceHSUDuOvy5I1YoCUgUH4Gw5zmTrbWIHO1nUE38dp7t0gQsnj2aeeWfGM0XxnOA3BAt6PnqTskVorWh2PChWBCtS8lrhh8UK40qUsq7qk-JJSluMsWISPy5OqswSLsSq-JluPl2sz5BBX4bblpTOTxCNnZzfoCkan2x04-SCR132hniGXELO70K_gzYbyJrYOmNRCzvowziAn5DxLUo30MNkejTMyfaANjH8mK7vQhE24HOVRfZp8agzfYJnh_e0-Hb57uv6Q3n1-f3H9cVVaZniU8klNNxQKzmuurqiFkyrBDcNp7JpWQPAWiyUrZkVXZtDikIHnAohAIi09LR4u9cd52aA1uY2o-n1GN1g4q0Oxum_I95d603Y6UopXtciC7w-CMTwfYY06cElC31vPIQ5aSlqIgmt8P_JvB1GKOGZfPUPuQ1z9PkftCRMScKZzND5HrIxpBShu2-aYL0cgV6OQB-PIGe8_HPWe_731jOADsCSeZQTupa6woItQ7zYI9uUt36UYIJlBUZ_AZ4bxLo</recordid><startdate>20101130</startdate><enddate>20101130</enddate><creator>Park, Chong Yon</creator><creator>Pierce, Stephanie A.</creator><creator>von Drehle, Morgan</creator><creator>Ivey, Kathryn N.</creator><creator>Morgan, Jayson A.</creator><creator>Blau, Helen M.</creator><creator>Srivastava, Deepak</creator><creator>Olson, Eric N.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20101130</creationdate><title>skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration</title><author>Park, Chong Yon ; Pierce, Stephanie A. ; von Drehle, Morgan ; Ivey, Kathryn N. ; Morgan, Jayson A. ; Blau, Helen M. ; Srivastava, Deepak ; Olson, Eric N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-68eb6a3c8602f423cead976ab638bd5bee5d079c45c7fdd9793efe63777ee18c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adipocytes</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Artificial satellites</topic><topic>Biological Sciences</topic><topic>Body Patterning</topic><topic>Cardiac muscle</topic><topic>Cardiomyocytes</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Cell survival</topic><topic>Chromatin</topic><topic>Chromatin remodeling</topic><topic>Deoxyribonucleic acid</topic><topic>Development</topic><topic>Developmental biology</topic><topic>DNA</topic><topic>DNA-binding protein</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryo, Mammalian - pathology</topic><topic>Embryos</topic><topic>Gene deletion</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Targeting</topic><topic>Heart</topic><topic>Heart - growth & development</topic><topic>Heart Ventricles - abnormalities</topic><topic>Heart Ventricles - embryology</topic><topic>Heart Ventricles - pathology</topic><topic>histone methyltransferase</topic><topic>Hypoplasia</topic><topic>Injuries</topic><topic>Lethality</topic><topic>Mice</topic><topic>Molecular Chaperones - metabolism</topic><topic>Muscle Development - genetics</topic><topic>Muscle Development - physiology</topic><topic>Muscle Fibers, Skeletal - metabolism</topic><topic>Muscle Fibers, Skeletal - pathology</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Muscle, Skeletal - embryology</topic><topic>Muscle, Skeletal - growth & development</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscles</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Organ Specificity - genetics</topic><topic>Organogenesis - genetics</topic><topic>Protein Binding</topic><topic>Proteins</topic><topic>Regeneration - physiology</topic><topic>regulatory proteins</topic><topic>Rodents</topic><topic>satellite cells</topic><topic>Skeletal muscle</topic><topic>Skeletal muscle satellite cells</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Chong Yon</creatorcontrib><creatorcontrib>Pierce, Stephanie A.</creatorcontrib><creatorcontrib>von Drehle, Morgan</creatorcontrib><creatorcontrib>Ivey, Kathryn N.</creatorcontrib><creatorcontrib>Morgan, Jayson A.</creatorcontrib><creatorcontrib>Blau, Helen M.</creatorcontrib><creatorcontrib>Srivastava, Deepak</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Chong Yon</au><au>Pierce, Stephanie A.</au><au>von Drehle, Morgan</au><au>Ivey, Kathryn N.</au><au>Morgan, Jayson A.</au><au>Blau, Helen M.</au><au>Srivastava, Deepak</au><au>Olson, Eric N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2010-11-30</date><risdate>2010</risdate><volume>107</volume><issue>48</issue><spage>20750</spage><epage>20755</epage><pages>20750-20755</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC -/- adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC -/- mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>21071677</pmid><doi>10.1073/pnas.1013493107</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Animals Animals, Newborn Artificial satellites Biological Sciences Body Patterning Cardiac muscle Cardiomyocytes Cell growth Cell Proliferation Cell survival Chromatin Chromatin remodeling Deoxyribonucleic acid Development Developmental biology DNA DNA-binding protein DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Embryo, Mammalian - metabolism Embryo, Mammalian - pathology Embryos Gene deletion Gene expression regulation Gene Expression Regulation, Developmental Gene Targeting Heart Heart - growth & development Heart Ventricles - abnormalities Heart Ventricles - embryology Heart Ventricles - pathology histone methyltransferase Hypoplasia Injuries Lethality Mice Molecular Chaperones - metabolism Muscle Development - genetics Muscle Development - physiology Muscle Fibers, Skeletal - metabolism Muscle Fibers, Skeletal - pathology Muscle Proteins - genetics Muscle Proteins - metabolism Muscle, Skeletal - embryology Muscle, Skeletal - growth & development Muscle, Skeletal - pathology Muscles Myocardium - metabolism Myocardium - pathology Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Organ Specificity - genetics Organogenesis - genetics Protein Binding Proteins Regeneration - physiology regulatory proteins Rodents satellite cells Skeletal muscle Skeletal muscle satellite cells Transcription factors Transcription Factors - genetics Transcription Factors - metabolism |
| title | skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration |
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