Mutagenesis of the Myogenin Basic Region Identifies an Ancient Protein Motif Critical for Activation of Myogenesis
Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-dir...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-07, Vol.88 (13), p.5675-5679 |
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| creator | Brennan, Thomas J. Chakraborty, Tushar Olson, Eric N. |
| description | Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr87) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program. |
| doi_str_mv | 10.1073/pnas.88.13.5675 |
| format | Article |
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Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr87) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.13.5675</identifier><identifier>PMID: 1648228</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Animals ; Binding, Competitive ; Biological and medical sciences ; Cell Differentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cells ; DNA ; DNA Mutational Analysis ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - genetics ; Fundamental and applied biological sciences. Psychology ; Gels ; Gene activation ; Gene Expression Regulation ; Genetic mutation ; Mice ; Molecular and cellular biology ; Molecular Sequence Data ; Muscle development ; Muscle Proteins - chemistry ; Muscle Proteins - genetics ; Muscles - cytology ; Muscles - physiology ; Mutagenesis ; Myogenin ; Structure-Activity Relationship ; Transactivation ; Transcription, Genetic ; Transfection</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-07, Vol.88 (13), p.5675-5679</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c617t-a2be22e05ade326b48685b856c9672af8b4521ff0d8065286e9854a2f20d1ada3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/13.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2357241$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2357241$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4954167$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1648228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brennan, Thomas J.</creatorcontrib><creatorcontrib>Chakraborty, Tushar</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><title>Mutagenesis of the Myogenin Basic Region Identifies an Ancient Protein Motif Critical for Activation of Myogenesis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr87) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cells</subject><subject>DNA</subject><subject>DNA Mutational Analysis</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gels</subject><subject>Gene activation</subject><subject>Gene Expression Regulation</subject><subject>Genetic mutation</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Muscle development</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscle Proteins - genetics</subject><subject>Muscles - cytology</subject><subject>Muscles - physiology</subject><subject>Mutagenesis</subject><subject>Myogenin</subject><subject>Structure-Activity Relationship</subject><subject>Transactivation</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-PEyEcxYnRrHX17EUNB6On6QIDDCReauOPTbbRGD2Tb2egy2Y6VGA27n8vk6nVvXgi8D7vfb_hIfSckiUlTX1xGCAtlVrSeilkIx6gBSWaVpJr8hAtCGFNpTjjj9GTlG4IIVoocobOqOSKMbVAcTNm2NnBJp9wcDhfW7y5C-XFD_g9JN_ib3bnw4AvOztk77xNGAa8Glpf7vhrDNkWdBOKhtfRZ99Cj12IeNVmfwt58pbgOXQa8xQ9ctAn--x4nqMfHz98X3-urr58ulyvrqpW0iZXwLaWMUsEdLZmcsuVVGKrhGy1bBg4teWCUedIp4gUTEmrleDAHCMdhQ7qc_Ruzj2M273t2rJuhN4cot9DvDMBvLmvDP7a7MKtEVRzUuxvjvYYfo42ZbP3qbV9D4MNYzJUaC1qpgt4MYNtDClF604jKDFTSWYqyShlaG2mkorj5b-b_eXnVor--qhDKr_pIpTfTieMa8GpbAr26ohN-X_Ue3Pe_hcwbuz7bH_lQr6YyZuUQzyhrBYN47T-Dd1kvi8</recordid><startdate>19910701</startdate><enddate>19910701</enddate><creator>Brennan, Thomas J.</creator><creator>Chakraborty, Tushar</creator><creator>Olson, Eric N.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</scope><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19910701</creationdate><title>Mutagenesis of the Myogenin Basic Region Identifies an Ancient Protein Motif Critical for Activation of Myogenesis</title><author>Brennan, Thomas J. ; Chakraborty, Tushar ; Olson, Eric N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c617t-a2be22e05ade326b48685b856c9672af8b4521ff0d8065286e9854a2f20d1ada3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cells</topic><topic>DNA</topic><topic>DNA Mutational Analysis</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gels</topic><topic>Gene activation</topic><topic>Gene Expression Regulation</topic><topic>Genetic mutation</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Muscle development</topic><topic>Muscle Proteins - chemistry</topic><topic>Muscle Proteins - genetics</topic><topic>Muscles - cytology</topic><topic>Muscles - physiology</topic><topic>Mutagenesis</topic><topic>Myogenin</topic><topic>Structure-Activity Relationship</topic><topic>Transactivation</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brennan, Thomas J.</creatorcontrib><creatorcontrib>Chakraborty, Tushar</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</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>Brennan, Thomas J.</au><au>Chakraborty, Tushar</au><au>Olson, Eric N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutagenesis of the Myogenin Basic Region Identifies an Ancient Protein Motif Critical for Activation of Myogenesis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-07-01</date><risdate>1991</risdate><volume>88</volume><issue>13</issue><spage>5675</spage><epage>5679</epage><pages>5675-5679</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr87) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1648228</pmid><doi>10.1073/pnas.88.13.5675</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Amino acids Animals Binding, Competitive Biological and medical sciences Cell Differentiation Cell differentiation, maturation, development, hematopoiesis Cell physiology Cells DNA DNA Mutational Analysis DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics Fundamental and applied biological sciences. Psychology Gels Gene activation Gene Expression Regulation Genetic mutation Mice Molecular and cellular biology Molecular Sequence Data Muscle development Muscle Proteins - chemistry Muscle Proteins - genetics Muscles - cytology Muscles - physiology Mutagenesis Myogenin Structure-Activity Relationship Transactivation Transcription, Genetic Transfection |
| title | Mutagenesis of the Myogenin Basic Region Identifies an Ancient Protein Motif Critical for Activation of Myogenesis |
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