Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex
Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is requi...
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| Veröffentlicht in: | Nature cell biology 2008-01, Vol.10 (1), p.77-84 |
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| creator | McKinnell, Iain W Greenblatt, Jack F Rudnicki, Michael A Addicks, Gregory C Dilworth, F. Jeffrey Ishibashi, Jeff Le Grand, Fabien Punch, Vincent G. J |
| description | Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme. |
| doi_str_mv | 10.1038/ncb1671 |
| format | Article |
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Jeffrey ; Ishibashi, Jeff ; Le Grand, Fabien ; Punch, Vincent G. J</creator><creatorcontrib>McKinnell, Iain W ; Greenblatt, Jack F ; Rudnicki, Michael A ; Addicks, Gregory C ; Dilworth, F. Jeffrey ; Ishibashi, Jeff ; Le Grand, Fabien ; Punch, Vincent G. J</creatorcontrib><description>Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1671</identifier><identifier>PMID: 18066051</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cell Line ; Chromatin - metabolism ; Chromatin Immunoprecipitation ; Developmental Biology ; DNA binding proteins ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Electrophoresis, Polyacrylamide Gel ; Flow Cytometry ; Fluorescence ; Gene Expression Regulation ; Genes ; Genetic aspects ; Genetic regulation ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase - metabolism ; Histones - metabolism ; Immunoprecipitation ; letter ; Life Sciences ; Mass spectrometry ; Methylation ; Methyltransferases ; Mice ; Mice, Inbred C57BL ; Musculoskeletal system ; Myeloid-Lymphoid Leukemia Protein - genetics ; Myeloid-Lymphoid Leukemia Protein - metabolism ; Myoblasts - cytology ; Myoblasts - metabolism ; Myogenic Regulatory Factor 5 - genetics ; Myogenic Regulatory Factor 5 - metabolism ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oligonucleotide Array Sequence Analysis ; PAX7 Transcription Factor - genetics ; PAX7 Transcription Factor - metabolism ; Physiological aspects ; Protein Binding ; Protein Methyltransferases ; Proteins ; Proteins - genetics ; Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Small Interfering - genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stem Cells ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic</subject><ispartof>Nature cell biology, 2008-01, Vol.10 (1), p.77-84</ispartof><rights>Springer Nature Limited 2008</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c613t-478d547566c2c629fb152e27be6bc498735489760d559c2a3d0475b6821416c03</citedby><cites>FETCH-LOGICAL-c613t-478d547566c2c629fb152e27be6bc498735489760d559c2a3d0475b6821416c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18066051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McKinnell, Iain W</creatorcontrib><creatorcontrib>Greenblatt, Jack F</creatorcontrib><creatorcontrib>Rudnicki, Michael A</creatorcontrib><creatorcontrib>Addicks, Gregory C</creatorcontrib><creatorcontrib>Dilworth, F. Jeffrey</creatorcontrib><creatorcontrib>Ishibashi, Jeff</creatorcontrib><creatorcontrib>Le Grand, Fabien</creatorcontrib><creatorcontrib>Punch, Vincent G. J</creatorcontrib><title>Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Line</subject><subject>Chromatin - metabolism</subject><subject>Chromatin Immunoprecipitation</subject><subject>Developmental Biology</subject><subject>DNA binding proteins</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Flow Cytometry</subject><subject>Fluorescence</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic regulation</subject><subject>Histone Methyltransferases</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Histones - metabolism</subject><subject>Immunoprecipitation</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Mass spectrometry</subject><subject>Methylation</subject><subject>Methyltransferases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Musculoskeletal system</subject><subject>Myeloid-Lymphoid Leukemia Protein - genetics</subject><subject>Myeloid-Lymphoid Leukemia Protein - metabolism</subject><subject>Myoblasts - cytology</subject><subject>Myoblasts - metabolism</subject><subject>Myogenic Regulatory Factor 5 - genetics</subject><subject>Myogenic Regulatory Factor 5 - metabolism</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>PAX7 Transcription Factor - genetics</subject><subject>PAX7 Transcription Factor - metabolism</subject><subject>Physiological aspects</subject><subject>Protein Binding</subject><subject>Protein Methyltransferases</subject><subject>Proteins</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Small Interfering - genetics</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Stem Cells</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkmtrFDEUhgdR7EXxFyiDgpcPU5NMbvNFKMVLoaBY_RwymTO7KTPJmmTK7r9vlh1bV0UJ5Hae85Lz5hTFE4xOMKrlW2dazAW-VxxiKnhFuWjub_ecVaJuyEFxFOMVQphSJB4WB1gizhHDh8XlF70WpTbJXusEsRw3fgHOmjLP-dhuygAmTDaN4FLp-1KXSxuTd1COkJabIQXtYg9BRyiNH1cDrB8VD3o9RHg8r8fF9w_vv519qi4-fzw_O72oDMd1qqiQHaOCcW6I4aTpW8wIENECbw1tpKgZlY3gqGOsMUTXHcp0yyXBFHOD6uPi3U53NbUjdCa_MOhBrYIdddgor63ajzi7VAt_rUj2RGKaBV7NAsH_mCAmNdpoYBi0Az9FJTltGCGyzuTLf5ICYdGQGv0XJEjkqijL4PPfwCs_BZf9UoSQWjCGtmovdtBCD6Cs632uw2wV1SmWnMuGYpKpk79QeXQwWpO_qrf5fi_hzV5CZhKs00JPMarzy6_77OyRCT7GAP2tvxipbe-pufcy-ezX77jj5mbLwOsdEHPILSDclfyn1tMd6nSaAtxq_YzfAHYj6L8</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>McKinnell, Iain W</creator><creator>Greenblatt, Jack F</creator><creator>Rudnicki, Michael A</creator><creator>Addicks, Gregory C</creator><creator>Dilworth, F. 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Jeffrey</au><au>Ishibashi, Jeff</au><au>Le Grand, Fabien</au><au>Punch, Vincent G. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>10</volume><issue>1</issue><spage>77</spage><epage>84</epage><pages>77-84</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18066051</pmid><doi>10.1038/ncb1671</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biomedical and Life Sciences Cancer Research Cell Biology Cell Line Chromatin - metabolism Chromatin Immunoprecipitation Developmental Biology DNA binding proteins DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Electrophoresis, Polyacrylamide Gel Flow Cytometry Fluorescence Gene Expression Regulation Genes Genetic aspects Genetic regulation Histone Methyltransferases Histone-Lysine N-Methyltransferase - metabolism Histones - metabolism Immunoprecipitation letter Life Sciences Mass spectrometry Methylation Methyltransferases Mice Mice, Inbred C57BL Musculoskeletal system Myeloid-Lymphoid Leukemia Protein - genetics Myeloid-Lymphoid Leukemia Protein - metabolism Myoblasts - cytology Myoblasts - metabolism Myogenic Regulatory Factor 5 - genetics Myogenic Regulatory Factor 5 - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Oligonucleotide Array Sequence Analysis PAX7 Transcription Factor - genetics PAX7 Transcription Factor - metabolism Physiological aspects Protein Binding Protein Methyltransferases Proteins Proteins - genetics Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering - genetics Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stem Cells Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
| title | Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex |
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