Progress Update: Molecular Mechanism of p38 Kinase-mediated inhibition of DUX4

Our goal is to understand the molecular mechanism of p38-mediated DUX4 activation. Acquiring detailed knowledge of the multiple signaling pathways that “turn on” the DUX4 gene expression is essential to understand how FSHD develops and to identify unique characteristics of FSHD cells that can be targeted by novel therapies. Recently, we have identified a family of transcription factors that are involved in regulating the DUX4 gene. Using an siRNA approach, we have narrowed down key family members involved in DUX4 regulation. We are now in the process of generating CRISPR reagents and fluorescent reporter constructs. These reagents will allow us to carry out experiments to confirm the involvement of specific transcription factors in “turning on” DUX4. These experiments will provide important insights in understanding the biology of this family of transcription factors and their role in FSHD pathophysiology. These data may facilitate the identification of novel targets for FSHD.

See grant Molecular Mechanism of p38 Kinase-mediated inhibition of DUX4 Gene in Facioscapulohumeral Muscular Dystrophy