Posted by Friends of FSH Research on Nov 15, 2024
Report by Dr. Rajanikanth Vangipurapu & Dr. Fran Sverdrup
See also Uncovering the genetic drivers and suppressors of DUX4 in FSHD
Facioscapulohumeral muscular dystrophy (FSHD) is caused by mutations that compromise normal repression of the DUX4 gene in skeletal muscle. However, relatively little is known about the complex process of transcriptional activation (turning on) of the DUX4 gene. To develop targeted therapies for FSHD, a comprehensive understanding of how the DUX4 gene gets turned on is necessary. We have used a proteomics method (dCas9-APEX) to identify 291 proteins that specifically bind D4Z4 repeats (DUX4 regulatory region) when DUX4 is maximally activated during myogenic differentiation of FSHD patient-derived cells. These proteins are candidates for novel factors participating in turning on DUX4 in FSHD and will be evaluated using genetic depletion experiments.
Connect with us on social media