MEF2 and AP-1 transcription complexes have been individually implicated in myogenesis but their genetic interaction has not previously been addressed. Using MEF2A, c-Jun and Fra-1 ChIP-seq data and predicted AP-1 consensus motifs, we identified putative common MEF2 and AP-1 target genes, several of which are implicated in regulating the actin cytoskeleton. Since muscle atrophy results in remodelling or degradation of the actin cytoskeleton, we characterized the expression of putative MEF2/AP-1 target genes (Dstn, Flnc, Hspb7, Lmod3 and Plekhh2) under atrophic conditions using Dexamethasone (Dex) treatment in skeletal myoblasts. Hspb7 was induced by Dex treatment and further analyses revealed that loss of MEF2A using siRNA prevented Dex-regulated induction of Hspb7. Conversely, ectopic Fra-2 or c-Jun expression reduced Dex-mediated upregulation of Hspb7 while AP-1 depletion enhanced Hspb7 expression. In vivo, Hspb7 expression was upregulated, along with other autophagy-related genes, in response to atrophic conditions in mice. Manipulation of Hspb7 levels in mice also impacted gross muscle mass. Collectively, these data indicate that MEF2 and AP-1 confer antagonistic regulation of Hspb7 gene expression in skeletal muscle with implications for autophagy and muscle atrophy.
- Received March 29, 2016.
- Accepted September 8, 2016.
- © 2016. Published by The Company of Biologists Ltd