The expression of myogenic regulators, MyoD, myogenin, and p21WAF1/CIP1, was severely decreased in NF90 mice.
The competitive effect of Pax3 and Pax7 was also evident on the expression of myogenic regulators.
These Pax factors are the master myogenic regulators of embryonic and adult myogenesis, respectively (for review see [24]).
Taken together with our previous work [30], we conclude that Barx2 can form complexes with both positive (i.e. MyoD) and negative (i.e, Hes6) bHLH myogenic regulators.
Considering the toxic effects of mDUX expression, its interaction with myogenic regulators and inhibition of myogenic differentiation in both cell- and organism-based assays, we propose that the mouse D4Z4-like arrays represent a genetic unit functionally orthologous to the DUX4-bearing repeats at human 4q35.2.
In our previous work, we demonstrated that DUX4 and DUX4c both interfere with the expression of myogenic regulators and suggested that this was due to competitive binding between DUX and Pax proteins for the same regulatory sites in these genes.
However, despite the expression of these myogenic regulators, RMS is retained at different stages of myogenic differentiation.
10.7554/eLife.07343.013 Figure 4. MHC protein detected by immunostaining after perturbation of putative myogenic regulators.
10.7554/eLife.07343.018 Figure 5. Spatial analysis of gene expression after MO perturbation of selected putative myogenic regulators by FISH.
Consistent with this phenotypic observation, the induction of several master myogenic regulators (Myod1, Myog and Mef2c) was inhibited in the Huwe1 knockdown cells during differentiation.
