Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells
Rhabdomyosarcoma (RMS) is the commonest soft-tissue sarcoma in childhood and is characterized by expression of myogenic proteins, including the transcription factors MyoD and myogenin. There are two main subgroups, embryonal RMS and alveolar RMS (ARMS). Most ARMS are associated with chromosomal tran...
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| description | Rhabdomyosarcoma (RMS) is the commonest soft-tissue sarcoma in childhood and is characterized by expression of myogenic proteins, including the transcription factors MyoD and myogenin. There are two main subgroups, embryonal RMS and alveolar RMS (ARMS). Most ARMS are associated with chromosomal translocations that have breakpoints in introns of either
PAX3
or
PAX7
, and
FOXO1A
. These translocations create chimeric transcription factors termed PAX3/FOXO1A and PAX7/FOXO1A respectively. Upon ectopic PAX3/FOXO1A expression, together with other genetic manipulation in mice, both differentiating myoblasts and satellite cells (the resident stem cells of postnatal muscle) can give rise to tumours with ARMS characteristics. As PAX3 and PAX7 are part of transcriptional networks that regulate muscle stem cell function
in utero
and during early postnatal life, PAX3/FOXO1A and PAX7/FOXO1A may subvert normal PAX3 and PAX7 functions. Here we examined how PAX3/FOXO1A and PAX7/FOXO1A affect myogenesis in satellite cells. PAX3/FOXO1A or PAX7/FOXO1A inhibited myogenin expression and prevented terminal differentiation in murine satellite cells: the same effect as dominant-negative (DN) Pax3 or Pax7 constructs. The transcription of
MyoD
-target genes
myogenin
and
muscle creatine kinase
were suppressed by PAX3/FOXO1A or PAX7/FOXO1A in C2C12 myogenic cells again as seen with Pax3/7DN. PAX3/FOXO1A or PAX7/FOXO1A did not inhibit the transcriptional activity of MyoD by perturbing MyoD expression, localization, phosphorylation or interaction with E-proteins. Chromatin immunoprecipitation on the
myogenin
promoter showed that PAX3/FOXO1A or PAX7/FOXO1A did not prevent MyoD from binding. However, PAX3/FOXO1A or PAX7/FOXO1A reduced occupation of the
myogenin
promoter by RNA polymerase II and decreased acetylation of histone H4, but did not directly bind to the
myogenin
promoter. Together, these observations reveal that PAX3/FOXO1A and PAX7/FOXO1A act to prevent myogenic differentiation via suppression of the transcriptional activation of
MyoD
-target genes. |
| doi_str_mv | 10.1038/onc.2012.73 |
| format | Article |
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PAX3
or
PAX7
, and
FOXO1A
. These translocations create chimeric transcription factors termed PAX3/FOXO1A and PAX7/FOXO1A respectively. Upon ectopic PAX3/FOXO1A expression, together with other genetic manipulation in mice, both differentiating myoblasts and satellite cells (the resident stem cells of postnatal muscle) can give rise to tumours with ARMS characteristics. As PAX3 and PAX7 are part of transcriptional networks that regulate muscle stem cell function
in utero
and during early postnatal life, PAX3/FOXO1A and PAX7/FOXO1A may subvert normal PAX3 and PAX7 functions. Here we examined how PAX3/FOXO1A and PAX7/FOXO1A affect myogenesis in satellite cells. PAX3/FOXO1A or PAX7/FOXO1A inhibited myogenin expression and prevented terminal differentiation in murine satellite cells: the same effect as dominant-negative (DN) Pax3 or Pax7 constructs. The transcription of
MyoD
-target genes
myogenin
and
muscle creatine kinase
were suppressed by PAX3/FOXO1A or PAX7/FOXO1A in C2C12 myogenic cells again as seen with Pax3/7DN. PAX3/FOXO1A or PAX7/FOXO1A did not inhibit the transcriptional activity of MyoD by perturbing MyoD expression, localization, phosphorylation or interaction with E-proteins. Chromatin immunoprecipitation on the
myogenin
promoter showed that PAX3/FOXO1A or PAX7/FOXO1A did not prevent MyoD from binding. However, PAX3/FOXO1A or PAX7/FOXO1A reduced occupation of the
myogenin
promoter by RNA polymerase II and decreased acetylation of histone H4, but did not directly bind to the
myogenin
promoter. Together, these observations reveal that PAX3/FOXO1A and PAX7/FOXO1A act to prevent myogenic differentiation via suppression of the transcriptional activation of
MyoD
-target genes.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2012.73</identifier><identifier>PMID: 22710712</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337/572 ; 631/45/612/822 ; 631/532/2439 ; 692/699/67/1798 ; Acetylation ; Alveoli ; Animals ; Apoptosis ; Arm ; Breakpoints ; Cancer ; Cell Biology ; Cell differentiation ; Cell Differentiation - genetics ; Cell Line ; Children ; Chromatin ; Chromosome translocations ; Creatine ; Creatine kinase ; Creatine Kinase, MM Form - genetics ; Development and progression ; Differentiation ; DNA-directed RNA polymerase ; Forkhead Box Protein O1 ; Forkhead Transcription Factors - metabolism ; Gene expression ; Gene Expression Regulation ; Genetic aspects ; Genetic transcription ; Health aspects ; Histone H4 ; Human Genetics ; Immunoprecipitation ; Internal Medicine ; Introns ; Kinases ; Localization ; Medicine ; Medicine & Public Health ; Mice ; Muscle cells ; Muscles ; Myoblasts ; MyoD protein ; MyoD Protein - metabolism ; Myogenesis ; Myogenin ; Myogenin - genetics ; Oncogene Proteins, Fusion - metabolism ; Oncology ; original-article ; Paired Box Transcription Factors - metabolism ; Pax3 protein ; PAX3 Transcription Factor ; PAX7 Transcription Factor - metabolism ; Phosphorylation ; Physiological aspects ; Promoters ; Proteins ; Rhabdomyosarcoma ; Rhabdomyosarcoma, Alveolar - genetics ; RNA polymerase ; Sarcoma ; Satellite cells ; Satellite Cells, Skeletal Muscle - metabolism ; Stem cells ; Stem Cells - metabolism ; Transcription activation ; Transcription factors ; Tumors</subject><ispartof>Oncogene, 2013-01, Vol.32 (5), p.651-662</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 31, 2013</rights><rights>Macmillan Publishers Limited 2013.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-9b5d10e8cdd14af27ca82b6d0b9a82040d292e16a8f750894d08909c605ecf223</citedby><cites>FETCH-LOGICAL-c585t-9b5d10e8cdd14af27ca82b6d0b9a82040d292e16a8f750894d08909c605ecf223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2012.73$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2012.73$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22710712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Calhabeu, F</creatorcontrib><creatorcontrib>Hayashi, S</creatorcontrib><creatorcontrib>Morgan, J E</creatorcontrib><creatorcontrib>Relaix, F</creatorcontrib><creatorcontrib>Zammit, P S</creatorcontrib><title>Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Rhabdomyosarcoma (RMS) is the commonest soft-tissue sarcoma in childhood and is characterized by expression of myogenic proteins, including the transcription factors MyoD and myogenin. There are two main subgroups, embryonal RMS and alveolar RMS (ARMS). Most ARMS are associated with chromosomal translocations that have breakpoints in introns of either
PAX3
or
PAX7
, and
FOXO1A
. These translocations create chimeric transcription factors termed PAX3/FOXO1A and PAX7/FOXO1A respectively. Upon ectopic PAX3/FOXO1A expression, together with other genetic manipulation in mice, both differentiating myoblasts and satellite cells (the resident stem cells of postnatal muscle) can give rise to tumours with ARMS characteristics. As PAX3 and PAX7 are part of transcriptional networks that regulate muscle stem cell function
in utero
and during early postnatal life, PAX3/FOXO1A and PAX7/FOXO1A may subvert normal PAX3 and PAX7 functions. Here we examined how PAX3/FOXO1A and PAX7/FOXO1A affect myogenesis in satellite cells. PAX3/FOXO1A or PAX7/FOXO1A inhibited myogenin expression and prevented terminal differentiation in murine satellite cells: the same effect as dominant-negative (DN) Pax3 or Pax7 constructs. The transcription of
MyoD
-target genes
myogenin
and
muscle creatine kinase
were suppressed by PAX3/FOXO1A or PAX7/FOXO1A in C2C12 myogenic cells again as seen with Pax3/7DN. PAX3/FOXO1A or PAX7/FOXO1A did not inhibit the transcriptional activity of MyoD by perturbing MyoD expression, localization, phosphorylation or interaction with E-proteins. Chromatin immunoprecipitation on the
myogenin
promoter showed that PAX3/FOXO1A or PAX7/FOXO1A did not prevent MyoD from binding. However, PAX3/FOXO1A or PAX7/FOXO1A reduced occupation of the
myogenin
promoter by RNA polymerase II and decreased acetylation of histone H4, but did not directly bind to the
myogenin
promoter. Together, these observations reveal that PAX3/FOXO1A and PAX7/FOXO1A act to prevent myogenic differentiation via suppression of the transcriptional activation of
MyoD
-target genes.</description><subject>631/337/572</subject><subject>631/45/612/822</subject><subject>631/532/2439</subject><subject>692/699/67/1798</subject><subject>Acetylation</subject><subject>Alveoli</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Arm</subject><subject>Breakpoints</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Children</subject><subject>Chromatin</subject><subject>Chromosome translocations</subject><subject>Creatine</subject><subject>Creatine kinase</subject><subject>Creatine Kinase, MM Form - genetics</subject><subject>Development and progression</subject><subject>Differentiation</subject><subject>DNA-directed RNA polymerase</subject><subject>Forkhead Box Protein O1</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Health aspects</subject><subject>Histone H4</subject><subject>Human Genetics</subject><subject>Immunoprecipitation</subject><subject>Internal Medicine</subject><subject>Introns</subject><subject>Kinases</subject><subject>Localization</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Muscle cells</subject><subject>Muscles</subject><subject>Myoblasts</subject><subject>MyoD protein</subject><subject>MyoD Protein - metabolism</subject><subject>Myogenesis</subject><subject>Myogenin</subject><subject>Myogenin - genetics</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>Oncology</subject><subject>original-article</subject><subject>Paired Box Transcription Factors - metabolism</subject><subject>Pax3 protein</subject><subject>PAX3 Transcription Factor</subject><subject>PAX7 Transcription Factor - metabolism</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Promoters</subject><subject>Proteins</subject><subject>Rhabdomyosarcoma</subject><subject>Rhabdomyosarcoma, Alveolar - genetics</subject><subject>RNA polymerase</subject><subject>Sarcoma</subject><subject>Satellite cells</subject><subject>Satellite Cells, Skeletal Muscle - metabolism</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Transcription activation</subject><subject>Transcription factors</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkt9rFDEQxxdR7Fl98l0Cvgh1r0l2s7t5PGqrQuV8UOhbyCWz15Td5MxkC_en-N-a5VqpUkQCSSb5zHd-MEXxmtElo1V3GrxZcsr4sq2eFAtWt00phKyfFgsqBS0lr_hR8QLxhlLaSsqfF0ect4y2jC-Kn6vhFsKgI4nXemPDuA-oowmjLjViME4nsGQXQwLnkXxdXVWnF-urNVsR7e1st_c2TrtdBESSroGkqD2a6HbJBa8Hok1yty7tSejJl334UCYdt5DIFjwgcZ6ME5oBCCYYiYFhwJfFs14PCK_uzuPi-8X5t7NP5eX64-ez1WVpRCdSKTfCMgqdsZbVuuet0R3fNJZuZL7QmlouObBGd30raCdrmzcqTUMFmJ7z6rh4d9DNRf6YAJMaHc4ZaA9hQsW4ZM3caPYfaFe1FeuEzOjbv9CbMMXcCVS8qZngos6a_6CyFpeVaJoH1FYPoJzvQ-6umUOrVY5WZ4zVmVo-QuVlYXQmeOhdfv_D4eTgYGJAjNCrXXSjjnvFqJoLVnmy1DxZqq0y_eYu1Wkzgv3N3o9SBt4fAMxffgvxQS2P6P0CZ2bVAw</recordid><startdate>20130131</startdate><enddate>20130131</enddate><creator>Calhabeu, F</creator><creator>Hayashi, S</creator><creator>Morgan, J E</creator><creator>Relaix, F</creator><creator>Zammit, P S</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20130131</creationdate><title>Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells</title><author>Calhabeu, F ; Hayashi, S ; Morgan, J E ; Relaix, F ; Zammit, P S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-9b5d10e8cdd14af27ca82b6d0b9a82040d292e16a8f750894d08909c605ecf223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/337/572</topic><topic>631/45/612/822</topic><topic>631/532/2439</topic><topic>692/699/67/1798</topic><topic>Acetylation</topic><topic>Alveoli</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Arm</topic><topic>Breakpoints</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line</topic><topic>Children</topic><topic>Chromatin</topic><topic>Chromosome translocations</topic><topic>Creatine</topic><topic>Creatine kinase</topic><topic>Creatine Kinase, MM Form - genetics</topic><topic>Development and progression</topic><topic>Differentiation</topic><topic>DNA-directed RNA polymerase</topic><topic>Forkhead Box Protein O1</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Health aspects</topic><topic>Histone H4</topic><topic>Human Genetics</topic><topic>Immunoprecipitation</topic><topic>Internal Medicine</topic><topic>Introns</topic><topic>Kinases</topic><topic>Localization</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Muscle cells</topic><topic>Muscles</topic><topic>Myoblasts</topic><topic>MyoD protein</topic><topic>MyoD Protein - metabolism</topic><topic>Myogenesis</topic><topic>Myogenin</topic><topic>Myogenin - genetics</topic><topic>Oncogene Proteins, Fusion - metabolism</topic><topic>Oncology</topic><topic>original-article</topic><topic>Paired Box Transcription Factors - metabolism</topic><topic>Pax3 protein</topic><topic>PAX3 Transcription Factor</topic><topic>PAX7 Transcription Factor - metabolism</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Promoters</topic><topic>Proteins</topic><topic>Rhabdomyosarcoma</topic><topic>Rhabdomyosarcoma, Alveolar - genetics</topic><topic>RNA polymerase</topic><topic>Sarcoma</topic><topic>Satellite cells</topic><topic>Satellite Cells, Skeletal Muscle - metabolism</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Transcription activation</topic><topic>Transcription factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Calhabeu, F</creatorcontrib><creatorcontrib>Hayashi, S</creatorcontrib><creatorcontrib>Morgan, J E</creatorcontrib><creatorcontrib>Relaix, F</creatorcontrib><creatorcontrib>Zammit, P S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Calhabeu, F</au><au>Hayashi, S</au><au>Morgan, J E</au><au>Relaix, F</au><au>Zammit, P S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2013-01-31</date><risdate>2013</risdate><volume>32</volume><issue>5</issue><spage>651</spage><epage>662</epage><pages>651-662</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Rhabdomyosarcoma (RMS) is the commonest soft-tissue sarcoma in childhood and is characterized by expression of myogenic proteins, including the transcription factors MyoD and myogenin. There are two main subgroups, embryonal RMS and alveolar RMS (ARMS). Most ARMS are associated with chromosomal translocations that have breakpoints in introns of either
PAX3
or
PAX7
, and
FOXO1A
. These translocations create chimeric transcription factors termed PAX3/FOXO1A and PAX7/FOXO1A respectively. Upon ectopic PAX3/FOXO1A expression, together with other genetic manipulation in mice, both differentiating myoblasts and satellite cells (the resident stem cells of postnatal muscle) can give rise to tumours with ARMS characteristics. As PAX3 and PAX7 are part of transcriptional networks that regulate muscle stem cell function
in utero
and during early postnatal life, PAX3/FOXO1A and PAX7/FOXO1A may subvert normal PAX3 and PAX7 functions. Here we examined how PAX3/FOXO1A and PAX7/FOXO1A affect myogenesis in satellite cells. PAX3/FOXO1A or PAX7/FOXO1A inhibited myogenin expression and prevented terminal differentiation in murine satellite cells: the same effect as dominant-negative (DN) Pax3 or Pax7 constructs. The transcription of
MyoD
-target genes
myogenin
and
muscle creatine kinase
were suppressed by PAX3/FOXO1A or PAX7/FOXO1A in C2C12 myogenic cells again as seen with Pax3/7DN. PAX3/FOXO1A or PAX7/FOXO1A did not inhibit the transcriptional activity of MyoD by perturbing MyoD expression, localization, phosphorylation or interaction with E-proteins. Chromatin immunoprecipitation on the
myogenin
promoter showed that PAX3/FOXO1A or PAX7/FOXO1A did not prevent MyoD from binding. However, PAX3/FOXO1A or PAX7/FOXO1A reduced occupation of the
myogenin
promoter by RNA polymerase II and decreased acetylation of histone H4, but did not directly bind to the
myogenin
promoter. Together, these observations reveal that PAX3/FOXO1A and PAX7/FOXO1A act to prevent myogenic differentiation via suppression of the transcriptional activation of
MyoD
-target genes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22710712</pmid><doi>10.1038/onc.2012.73</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2013-01, Vol.32 (5), p.651-662 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1291610381 |
| source | MEDLINE; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online |
| subjects | 631/337/572 631/45/612/822 631/532/2439 692/699/67/1798 Acetylation Alveoli Animals Apoptosis Arm Breakpoints Cancer Cell Biology Cell differentiation Cell Differentiation - genetics Cell Line Children Chromatin Chromosome translocations Creatine Creatine kinase Creatine Kinase, MM Form - genetics Development and progression Differentiation DNA-directed RNA polymerase Forkhead Box Protein O1 Forkhead Transcription Factors - metabolism Gene expression Gene Expression Regulation Genetic aspects Genetic transcription Health aspects Histone H4 Human Genetics Immunoprecipitation Internal Medicine Introns Kinases Localization Medicine Medicine & Public Health Mice Muscle cells Muscles Myoblasts MyoD protein MyoD Protein - metabolism Myogenesis Myogenin Myogenin - genetics Oncogene Proteins, Fusion - metabolism Oncology original-article Paired Box Transcription Factors - metabolism Pax3 protein PAX3 Transcription Factor PAX7 Transcription Factor - metabolism Phosphorylation Physiological aspects Promoters Proteins Rhabdomyosarcoma Rhabdomyosarcoma, Alveolar - genetics RNA polymerase Sarcoma Satellite cells Satellite Cells, Skeletal Muscle - metabolism Stem cells Stem Cells - metabolism Transcription activation Transcription factors Tumors |
| title | Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T06%3A03%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alveolar%20rhabdomyosarcoma-associated%20proteins%20PAX3/FOXO1A%20and%20PAX7/FOXO1A%20suppress%20the%20transcriptional%20activity%20of%20MyoD-target%20genes%20in%20muscle%20stem%20cells&rft.jtitle=Oncogene&rft.au=Calhabeu,%20F&rft.date=2013-01-31&rft.volume=32&rft.issue=5&rft.spage=651&rft.epage=662&rft.pages=651-662&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2012.73&rft_dat=%3Cgale_proqu%3EA318493514%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1282935660&rft_id=info:pmid/22710712&rft_galeid=A318493514&rfr_iscdi=true |