The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy
| Autor: | Charis L. Himeda, Peter L. Jones |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
Chromosomal Proteins Non-Histone Severity of Illness Index Epigenesis Genetic DUX4 Genetics Humans Medicine Facioscapulohumeral muscular dystrophy DNA (Cytosine-5-)-Methyltransferases Epigenetics Muscular dystrophy Muscle Skeletal Myopathy Molecular Biology Genetics (clinical) Gene Editing Homeodomain Proteins Genome Human business.industry Skeletal muscle DNA Methylation medicine.disease Chromatin Muscular Dystrophy Facioscapulohumeral medicine.anatomical_structure Genetic Loci Mutation CRISPR-Cas Systems Chromosomes Human Pair 4 medicine.symptom business |
| Zdroj: | Annual Review of Genomics and Human Genetics. 20:265-291 |
| ISSN: | 1545-293X 1527-8204 |
| DOI: | 10.1146/annurev-genom-083118-014933 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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