The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein
Abstract Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene ca...
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| Veröffentlicht in: | Neuromuscular disorders : NMD 2007-08, Vol.17 (8), p.611-623 |
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| creator | Kowaljow, Valeria Marcowycz, Aline Ansseau, Eugénie Conde, Cecilia B Sauvage, Sébastien Mattéotti, Christel Arias, Cristina Corona, E. Daniel Nuñez, Nicolás G Leo, Oberdan Wattiez, Ruddy Figlewicz, Denise Laoudj-Chenivesse, Dalila Belayew, Alexandra Coppée, Frédérique Rosa, Alberto L |
| description | Abstract Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4 . We identified DUX4 mRNAs in cells transfected with genomic fragments containing the DUX4 gene. Using RT-PCR we also recognized expressed DUX4 mRNAs in primary FSHD myoblasts. Polyclonal antibodies raised against specific DUX4 peptides detected the DUX4 protein in cells transfected with D4Z4 elements. DUX4 localizes in the nucleus of cells transfected with CMV – DUX4 expression vectors. A DUX4-related protein is endogenously expressed in nuclei of adult and fetal human rhabdomyosarcoma cell lines. Overexpression of DUX4 induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope. We propose that DUX4-mediated cell death contributes to the pathogenic pathway in FSHD. |
| doi_str_mv | 10.1016/j.nmd.2007.04.002 |
| format | Article |
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Daniel ; Nuñez, Nicolás G ; Leo, Oberdan ; Wattiez, Ruddy ; Figlewicz, Denise ; Laoudj-Chenivesse, Dalila ; Belayew, Alexandra ; Coppée, Frédérique ; Rosa, Alberto L</creator><creatorcontrib>Kowaljow, Valeria ; Marcowycz, Aline ; Ansseau, Eugénie ; Conde, Cecilia B ; Sauvage, Sébastien ; Mattéotti, Christel ; Arias, Cristina ; Corona, E. Daniel ; Nuñez, Nicolás G ; Leo, Oberdan ; Wattiez, Ruddy ; Figlewicz, Denise ; Laoudj-Chenivesse, Dalila ; Belayew, Alexandra ; Coppée, Frédérique ; Rosa, Alberto L</creatorcontrib><description>Abstract Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4 . We identified DUX4 mRNAs in cells transfected with genomic fragments containing the DUX4 gene. Using RT-PCR we also recognized expressed DUX4 mRNAs in primary FSHD myoblasts. Polyclonal antibodies raised against specific DUX4 peptides detected the DUX4 protein in cells transfected with D4Z4 elements. DUX4 localizes in the nucleus of cells transfected with CMV – DUX4 expression vectors. A DUX4-related protein is endogenously expressed in nuclei of adult and fetal human rhabdomyosarcoma cell lines. Overexpression of DUX4 induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope. We propose that DUX4-mediated cell death contributes to the pathogenic pathway in FSHD.</description><identifier>ISSN: 0960-8966</identifier><identifier>EISSN: 1873-2364</identifier><identifier>DOI: 10.1016/j.nmd.2007.04.002</identifier><identifier>PMID: 17588759</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Amino Acid Sequence ; Apoptosis ; Apoptosis - physiology ; Cell Line, Tumor ; DUX4 ; FSHD ; Gene Expression - physiology ; Homeobox ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Life Sciences ; Membrane Proteins - metabolism ; Molecular Sequence Data ; Muscle ; Muscle Cells - cytology ; Muscle Cells - physiology ; Muscular Dystrophy, Facioscapulohumeral - genetics ; Muscular Dystrophy, Facioscapulohumeral - pathology ; Muscular Dystrophy, Facioscapulohumeral - physiopathology ; Neurology ; Nuclear Envelope - metabolism ; Nuclear Proteins - metabolism ; Quadriceps Muscle - cytology ; Rhabdomyosarcoma ; RNA, Messenger - metabolism ; Transcription, Genetic - physiology</subject><ispartof>Neuromuscular disorders : NMD, 2007-08, Vol.17 (8), p.611-623</ispartof><rights>Elsevier B.V.</rights><rights>2007 Elsevier B.V.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4642-5881c38a3ed0aa03f14a792ea2158ea21a8c85cf52546b3b7d171f1b299245713</citedby><cites>FETCH-LOGICAL-c4642-5881c38a3ed0aa03f14a792ea2158ea21a8c85cf52546b3b7d171f1b299245713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960896607001216$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17588759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03821105$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Kowaljow, Valeria</creatorcontrib><creatorcontrib>Marcowycz, Aline</creatorcontrib><creatorcontrib>Ansseau, Eugénie</creatorcontrib><creatorcontrib>Conde, Cecilia B</creatorcontrib><creatorcontrib>Sauvage, Sébastien</creatorcontrib><creatorcontrib>Mattéotti, Christel</creatorcontrib><creatorcontrib>Arias, Cristina</creatorcontrib><creatorcontrib>Corona, E. Daniel</creatorcontrib><creatorcontrib>Nuñez, Nicolás G</creatorcontrib><creatorcontrib>Leo, Oberdan</creatorcontrib><creatorcontrib>Wattiez, Ruddy</creatorcontrib><creatorcontrib>Figlewicz, Denise</creatorcontrib><creatorcontrib>Laoudj-Chenivesse, Dalila</creatorcontrib><creatorcontrib>Belayew, Alexandra</creatorcontrib><creatorcontrib>Coppée, Frédérique</creatorcontrib><creatorcontrib>Rosa, Alberto L</creatorcontrib><title>The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein</title><title>Neuromuscular disorders : NMD</title><addtitle>Neuromuscul Disord</addtitle><description>Abstract Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4 . We identified DUX4 mRNAs in cells transfected with genomic fragments containing the DUX4 gene. Using RT-PCR we also recognized expressed DUX4 mRNAs in primary FSHD myoblasts. Polyclonal antibodies raised against specific DUX4 peptides detected the DUX4 protein in cells transfected with D4Z4 elements. DUX4 localizes in the nucleus of cells transfected with CMV – DUX4 expression vectors. A DUX4-related protein is endogenously expressed in nuclei of adult and fetal human rhabdomyosarcoma cell lines. Overexpression of DUX4 induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope. We propose that DUX4-mediated cell death contributes to the pathogenic pathway in FSHD.</description><subject>Amino Acid Sequence</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Cell Line, Tumor</subject><subject>DUX4</subject><subject>FSHD</subject><subject>Gene Expression - physiology</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Muscle</subject><subject>Muscle Cells - cytology</subject><subject>Muscle Cells - physiology</subject><subject>Muscular Dystrophy, Facioscapulohumeral - genetics</subject><subject>Muscular Dystrophy, Facioscapulohumeral - pathology</subject><subject>Muscular Dystrophy, Facioscapulohumeral - physiopathology</subject><subject>Neurology</subject><subject>Nuclear Envelope - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Quadriceps Muscle - cytology</subject><subject>Rhabdomyosarcoma</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription, Genetic - physiology</subject><issn>0960-8966</issn><issn>1873-2364</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1r3DAQhkVpaDZJf0AvxadCDnZmZOvDFApL0nQLCzkkgd6EVh432nqtrWUH8u8rs0sKPfQioeGZV9IzjH1AKBBQXm2LftcUHEAVUBUA_A1boFZlzktZvWULqCXkupbylJ3FuAVAoaR6x05RCa2VqBds-fBE2c3jjyr7ST1ldszGVLi9X93gMuuCm2JGvQsNxcxm-yHkdh_2Yxi9m08j-f6CnbS2i_T-uJ-zx9uvD9erfH337fv1cp27SlY8TxeiK7UtqQFroWyxsqrmZDkKPa9WOy1cK7io5KbcqAYVtrjhdc0robA8Z5eH3Cfbmf3gd3Z4McF6s1quzVyDUnNEEM8z--nApjf-niiOZuejo66zPYUpGgUKBFcigXgA3RBiHKh9TUYws2OzNcmxmR0bqExynHo-HsOnzY6avx1HqQn4fAAo6Xj2NJjofLJIjR_IjaYJ_r_xX_7pdp3vvbPdL3qhuA3T0CfPBk3kBsz9POR5xulLgBxl-Qdtwp0M</recordid><startdate>200708</startdate><enddate>200708</enddate><creator>Kowaljow, Valeria</creator><creator>Marcowycz, Aline</creator><creator>Ansseau, Eugénie</creator><creator>Conde, Cecilia B</creator><creator>Sauvage, Sébastien</creator><creator>Mattéotti, Christel</creator><creator>Arias, Cristina</creator><creator>Corona, E. 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Daniel</au><au>Nuñez, Nicolás G</au><au>Leo, Oberdan</au><au>Wattiez, Ruddy</au><au>Figlewicz, Denise</au><au>Laoudj-Chenivesse, Dalila</au><au>Belayew, Alexandra</au><au>Coppée, Frédérique</au><au>Rosa, Alberto L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein</atitle><jtitle>Neuromuscular disorders : NMD</jtitle><addtitle>Neuromuscul Disord</addtitle><date>2007-08</date><risdate>2007</risdate><volume>17</volume><issue>8</issue><spage>611</spage><epage>623</epage><pages>611-623</pages><issn>0960-8966</issn><eissn>1873-2364</eissn><abstract>Abstract Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4 . 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| identifier | ISSN: 0960-8966 |
| ispartof | Neuromuscular disorders : NMD, 2007-08, Vol.17 (8), p.611-623 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amino Acid Sequence Apoptosis Apoptosis - physiology Cell Line, Tumor DUX4 FSHD Gene Expression - physiology Homeobox Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Life Sciences Membrane Proteins - metabolism Molecular Sequence Data Muscle Muscle Cells - cytology Muscle Cells - physiology Muscular Dystrophy, Facioscapulohumeral - genetics Muscular Dystrophy, Facioscapulohumeral - pathology Muscular Dystrophy, Facioscapulohumeral - physiopathology Neurology Nuclear Envelope - metabolism Nuclear Proteins - metabolism Quadriceps Muscle - cytology Rhabdomyosarcoma RNA, Messenger - metabolism Transcription, Genetic - physiology |
| title | The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein |
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