Functional role of MAFF in EPS-induced gene networks in C2C12 myotubes

Here we show that MAFF, a small Maf transcription factor, is consistently induced by acute exercise in both human and mouse skeletal muscle, with induction restricted to muscles recruited by the exercise protocol. In C2C12 cells, Maff increased during myogenic differentiation and was further induced by electrical pulse stimulation.

Using CRISPR/Cas9-mediated Maff knockout C2C12 cells, we found that loss of Maff did not change myosin heavy chain abundance or myotube size, but reduced myogenic fusion with accumulation of unfused nuclei. RNA sequencing revealed broad reprogramming in Maff-deficient myotubes, including reduced expression of muscle structural and contractile genes and increased interferon/immune responses and extracellular matrix-related signatures.