Facioscapulohumeral muscular dystrophy as a model for epigenetic regulation and disease

UMMS Affiliation

Department of Cell and Developmental Biology; Department of Neurology

Publication Date


Document Type



Animals; Disease Progression; Epigenesis, Genetic; Humans; Muscular Dystrophy, Facioscapulohumeral


Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics | Musculoskeletal Diseases | Nervous System Diseases


SIGNIFICANCE: Aberrant epigenetic regulation is an integral aspect of many diseases and complex disorders. Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, is caused by disrupted genetic and epigenetic regulation of a macrosatellite repeat. FSHD provides a powerful model to investigate disease-relevant epigenetic modifiers and general mechanisms of epigenetic regulation that govern gene expression.

RECENT ADVANCES: In the context of a genetically permissive allele, the one aspect of FSHD that is consistent across all known cases is the aberrant epigenetic state of the disease locus. In addition, certain mutations in the chromatin regulator SMCHD1 (structural maintenance of chromosomes hinge-domain protein 1) are sufficient to cause FSHD2 and enhance disease severity in FSHD1. Thus, there are multiple pathways to generate the epigenetic dysregulation required for FSHD.

CRITICAL ISSUES: Why do some individuals with the genetic requirements for FSHD develop disease pathology, while others remain asymptomatic? Similarly, disease progression is highly variable among individuals. What are the relative contributions of genetic background and environmental factors in determining disease manifestation, progression, and severity in FSHD? What is the interplay between epigenetic factors regulating the disease locus and which, if any, are viable therapeutic targets?

FUTURE DIRECTIONS: Epigenetic regulation represents a potentially powerful therapeutic target for FSHD. Determining the epigenetic signatures that are predictive of disease severity and identifying the spectrum of disease modifiers in FSHD are vital to the development of effective therapies.

DOI of Published Version



Himeda CL, Jones TI, Jones PL. Facioscapulohumeral muscular dystrophy as a model for epigenetic regulation and disease. Antioxid Redox Signal. 2015 Jun 1;22(16):1463-82. doi: 10.1089/ars.2014.6090. Epub 2014 Dec 4. Review. PubMed PMID: 25336259; PubMed Central PMCID: PMC4432493. Link to article on publisher's site

Journal/Book/Conference Title

Antioxidants and redox signaling

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