Daniel G. Miller MD PhD
Galina Filippova PhD
Friends of FSH Research and FSHD Canada Foundation are pleased to support the Daniel G. Miller MD PhD & Galina Filippova PhD project entitled "Identification of Chromatin Modifier Genes Important for DUX4 Silencing."
$50,000 for 1 year
Facioscapulohumeral Muscular Dystrophy is a dominantly inherited myopathy associated with chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4. DUX4 is encoded within each unit of the D4Z4 array where it is normally transcriptionally silenced and packaged as constitutive heterochromatin. Truncation of the array to less than 11 D4Z4 units (FSHD1) or mutations in SMCHD1 (FSHD2) results in chromatin relaxation and a small percentage of cultured myoblasts from these individuals exhibit infrequent bursts of DUX4 expression. This proposal builds on the hypothesis that epigenetic modification of D4Z4 chromatin structure is an important strategy for disease treatment. Here we propose to construct a library of siRNA’s that target genes involved in chromatin modification and examine the effect of reducing transcript levels on DUX4 gene expression to determine integral components of the DUX4 transcriptional silencing machinery.
See 2013 grant on Identification of Chromatin Modifier Genes Important for DUX4 Silencing.