Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disease for which no cure is available. FSHD is caused by the misexpression of the transcription factor DUX4 in skeletal muscle. We have identified a novel factor that is involved in the prevention of DUX4 expression in skeletal muscle. This novel factor was also found to be mutated in an FSHD patient for whom the genetic underpinnings were unknown. In this project we aim to confirm that this factor is indeed a new FSHD gene and to understand its mechanism of action in repressing DUX4 in skeletal muscle.
We apply genetic, biochemical, molecular and cellular techniques to patient- and control-derived muscle cells to validate our findings of this factor as a novel disease gene. We study the genome-wide role of this factor in controlling gene expression in muscle and non-muscle cells and correlate our findings to those of known FSHD genes.
This study will advance our knowledge of the different genetic causes of FSHD and contribute to a better understanding of the regulation of DUX4. This may help to define new therapeutic targets.
Financiering: Prinses Beatrix Spierfonds