(A) A fragment of the MLN promoter (−506 to +86, relative to the transcriptional start site) containing a highly conserved MyoD E-box (CACCTG) and MEF2 site (CTAATAACAG) was cloned in front of the luciferase reporter gene (MLN-Luc). The MLN-Luc reporter was robustly transactivated by the skeletal muscle transcription factors MyoD and MEF2 in COS7 cells (gray and red bars respectively). Mutation of the E-box (acCCgt) or Mef2 site (CTgggAACAG) (indicated by an X) abrogated transactivation by MyoD:E12 heterodimer or Mef2c, respectively. All luciferase values were normalized to the transactivation of a basal luciferase reporter (TATA-Luc) with MyoD or Mef2, respectively.
(B) Transfection of the MLN-Luc reporter or mutant luciferase vectors into C2C12 myoblasts or myotubes showed they are essential for the transactivation of the MLN promoter.
(C) X-gal and H&E staining of E10.5 mouse embryos harboring either the MLN promoter-lacZ transgene (WT) or mutations in the MLN promoter (ΔMef2 or ΔE-box). The MLN-promoter showed expression in the myotomal compartment of the somites (orange arrow) and premyogenic cells in the mandibular arch (red arrow). Mutation of the MEF2 or E-box sequences in the MLN promoter-lacZ transgene abrogated or abolished muscle specific expression.
See also Figure S4.