The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy
Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by con...
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| Veröffentlicht in: | Annual review of genomics and human genetics 2019-08, Vol.20 (1), p.265-291 |
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| creator | Himeda, Charis L Jones, Peter L |
| description | Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, aberrant expression of the
DUX4
gene in skeletal muscle. DUX4 is a pioneer transcription factor that activates a program of gene expression during early human development, after which its expression is silenced in most somatic cells. When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology. Epigenetic regulators of the disease locus represent particularly attractive therapeutic targets for FSHD, as many are not global modifiers of the genome, and altering their expression or activity should allow correction of the underlying defect. |
| doi_str_mv | 10.1146/annurev-genom-083118-014933 |
| format | Article |
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DUX4
gene in skeletal muscle. DUX4 is a pioneer transcription factor that activates a program of gene expression during early human development, after which its expression is silenced in most somatic cells. When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology. Epigenetic regulators of the disease locus represent particularly attractive therapeutic targets for FSHD, as many are not global modifiers of the genome, and altering their expression or activity should allow correction of the underlying defect.</description><identifier>ISSN: 1527-8204</identifier><identifier>EISSN: 1545-293X</identifier><identifier>DOI: 10.1146/annurev-genom-083118-014933</identifier><identifier>PMID: 31018108</identifier><language>eng</language><publisher>United States: Annual Reviews</publisher><subject>Chromatin ; Chromatin - chemistry ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - metabolism ; Chromosomes, Human, Pair 4 ; Contraction ; CRISPR-Cas Systems ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA Methylation ; DNA Methyltransferase 3B ; DUX4 ; Epigenesis, Genetic ; Epigenetics ; facioscapulohumeral muscular dystrophy ; FSHD ; Gene Editing ; Gene expression ; Genetic Loci ; Genome, Human ; Genomes ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscular dystrophy ; Muscular Dystrophy, Facioscapulohumeral - classification ; Muscular Dystrophy, Facioscapulohumeral - genetics ; Muscular Dystrophy, Facioscapulohumeral - metabolism ; Muscular Dystrophy, Facioscapulohumeral - pathology ; Musculoskeletal system ; Mutation ; Myopathy ; Severity of Illness Index ; Skeletal muscle ; Somatic cells ; Therapeutic applications</subject><ispartof>Annual review of genomics and human genetics, 2019-08, Vol.20 (1), p.265-291</ispartof><rights>Copyright Annual Reviews, Inc. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a525t-9046f2573b7c37f8a0c21136cbdc2aad629cf3eb7e3bc1c73d32d8c4577637013</citedby><cites>FETCH-LOGICAL-a525t-9046f2573b7c37f8a0c21136cbdc2aad629cf3eb7e3bc1c73d32d8c4577637013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.annualreviews.org/content/journals/10.1146/annurev-genom-083118-014933?crawler=true&mimetype=application/pdf$$EPDF$$P50$$Gannualreviews$$H</linktopdf><linktohtml>$$Uhttps://www.annualreviews.org/content/journals/10.1146/annurev-genom-083118-014933$$EHTML$$P50$$Gannualreviews$$H</linktohtml><link.rule.ids>70,314,776,780,4168,27901,27902,78223,78224</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31018108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Himeda, Charis L</creatorcontrib><creatorcontrib>Jones, Peter L</creatorcontrib><title>The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy</title><title>Annual review of genomics and human genetics</title><addtitle>Annu Rev Genomics Hum Genet</addtitle><description>Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, aberrant expression of the
DUX4
gene in skeletal muscle. DUX4 is a pioneer transcription factor that activates a program of gene expression during early human development, after which its expression is silenced in most somatic cells. When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology. Epigenetic regulators of the disease locus represent particularly attractive therapeutic targets for FSHD, as many are not global modifiers of the genome, and altering their expression or activity should allow correction of the underlying defect.</description><subject>Chromatin</subject><subject>Chromatin - chemistry</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Chromosomes, Human, Pair 4</subject><subject>Contraction</subject><subject>CRISPR-Cas Systems</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA Methylation</subject><subject>DNA Methyltransferase 3B</subject><subject>DUX4</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>facioscapulohumeral muscular dystrophy</subject><subject>FSHD</subject><subject>Gene Editing</subject><subject>Gene expression</subject><subject>Genetic Loci</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular dystrophy</subject><subject>Muscular Dystrophy, Facioscapulohumeral - classification</subject><subject>Muscular Dystrophy, Facioscapulohumeral - genetics</subject><subject>Muscular Dystrophy, Facioscapulohumeral - metabolism</subject><subject>Muscular Dystrophy, Facioscapulohumeral - pathology</subject><subject>Musculoskeletal system</subject><subject>Mutation</subject><subject>Myopathy</subject><subject>Severity of Illness Index</subject><subject>Skeletal muscle</subject><subject>Somatic cells</subject><subject>Therapeutic applications</subject><issn>1527-8204</issn><issn>1545-293X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE1LxDAQhoMofv8FKXjxUp1J2ibFi7K6q6B4WcFbSNPUrbRNTTbK_nu7dvXgzdPMwDPvDA8hpwjniEl2obouOPMRv5rOtjEIhihiwCRnbIvsY5qkMc3Zy_a6pzwWFJI9cuD9GwAIkcAu2WMIKBDEPpnOFyaamc4sa-0j1ZXRbV-__sy2iqZK19Zr1YfGLkJrnGqix-B1aJSLblZ-6Wy_WB2RnUo13hxv6iF5nt7OJ3fxw9PsfnL9EKuUpss4hySraMpZwTXjlVCgKSLLdFFqqlSZ0VxXzBTcsEKj5qxktBQ6STnPGAdkh-RszO2dfQ_GL2Vbe22aRnXGBi8pxRRoQvNsQE__oG82uG74bqAEhxSQrqnLkdLOeu9MJXtXt8qtJIJc65Yb3fJbtxx1y1H3sH2yuRGK1pS_uz9-B-BqBNYpqhlyavPp_3XjC0EdlTo</recordid><startdate>20190831</startdate><enddate>20190831</enddate><creator>Himeda, Charis L</creator><creator>Jones, Peter L</creator><general>Annual Reviews</general><general>Annual Reviews, Inc</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20190831</creationdate><title>The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy</title><author>Himeda, Charis L ; Jones, Peter L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a525t-9046f2573b7c37f8a0c21136cbdc2aad629cf3eb7e3bc1c73d32d8c4577637013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Chromatin</topic><topic>Chromatin - chemistry</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>Chromosomes, Human, Pair 4</topic><topic>Contraction</topic><topic>CRISPR-Cas Systems</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA Methylation</topic><topic>DNA Methyltransferase 3B</topic><topic>DUX4</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>facioscapulohumeral muscular dystrophy</topic><topic>FSHD</topic><topic>Gene Editing</topic><topic>Gene expression</topic><topic>Genetic Loci</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular dystrophy</topic><topic>Muscular Dystrophy, Facioscapulohumeral - classification</topic><topic>Muscular Dystrophy, Facioscapulohumeral - genetics</topic><topic>Muscular Dystrophy, Facioscapulohumeral - metabolism</topic><topic>Muscular Dystrophy, Facioscapulohumeral - pathology</topic><topic>Musculoskeletal system</topic><topic>Mutation</topic><topic>Myopathy</topic><topic>Severity of Illness Index</topic><topic>Skeletal muscle</topic><topic>Somatic cells</topic><topic>Therapeutic applications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Himeda, Charis L</creatorcontrib><creatorcontrib>Jones, Peter L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Annual review of genomics and human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Himeda, Charis L</au><au>Jones, Peter L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy</atitle><jtitle>Annual review of genomics and human genetics</jtitle><addtitle>Annu Rev Genomics Hum Genet</addtitle><date>2019-08-31</date><risdate>2019</risdate><volume>20</volume><issue>1</issue><spage>265</spage><epage>291</epage><pages>265-291</pages><issn>1527-8204</issn><eissn>1545-293X</eissn><abstract>Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, aberrant expression of the
DUX4
gene in skeletal muscle. DUX4 is a pioneer transcription factor that activates a program of gene expression during early human development, after which its expression is silenced in most somatic cells. When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology. Epigenetic regulators of the disease locus represent particularly attractive therapeutic targets for FSHD, as many are not global modifiers of the genome, and altering their expression or activity should allow correction of the underlying defect.</abstract><cop>United States</cop><pub>Annual Reviews</pub><pmid>31018108</pmid><doi>10.1146/annurev-genom-083118-014933</doi><tpages>27</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Chromatin Chromatin - chemistry Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism Chromosomes, Human, Pair 4 Contraction CRISPR-Cas Systems DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - metabolism DNA Methylation DNA Methyltransferase 3B DUX4 Epigenesis, Genetic Epigenetics facioscapulohumeral muscular dystrophy FSHD Gene Editing Gene expression Genetic Loci Genome, Human Genomes Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular dystrophy Muscular Dystrophy, Facioscapulohumeral - classification Muscular Dystrophy, Facioscapulohumeral - genetics Muscular Dystrophy, Facioscapulohumeral - metabolism Muscular Dystrophy, Facioscapulohumeral - pathology Musculoskeletal system Mutation Myopathy Severity of Illness Index Skeletal muscle Somatic cells Therapeutic applications |
| title | The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy |
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