friends of FSH Research

Funding Research for
FSH Muscular Dystrophy Dots

Mechanism of Wnt Signaling in Facioscapulohumeral Muscular

Posted by George Shaw on November 20, 2011

Gregory Block
Gregory Block

Progress update:

The gene thought to cause FSHD, Double Homeobox Protein 4 (DUX4), is unusual because it is encoded within each unit (D4Z4) of large arrays present on chromosomes 4 and 10. Normally the arrays are longer than 10 units and do not produce stable DUX4 transcripts. In people with FSHD, one of the chromosome 4 arrays becomes shortened and DUX4 transcripts and protein can be detected from cultured muscle cells and tissue. RNA and protein, however, are only present in a small fraction of muscle cells suggesting that additional constraints limit DUX4 production. I am interested in discovering ways to assay transcriptional activity of D4Z4, and to understand the factors that lead to activation of DUX4. I have developed multiple assays that allow us to understand the regulation of D4Z4 sequences in the context of development and myogenesis. I have identified signaling pathways that modulate transcription from D4Z4 and that can enhance or reduce the expression of DUX4.

—Gregory Block