Tceal7 has been identified as a direct, downstream target gene of MRF in the skeletal muscle. The overexpression of Tceal7 represses myogenic proliferation and promotes cell differentiation. Previous studies have defined the 0.7 kb upstream fragment of the Tceal7 gene. In the present study, we have further determined two clusters of transcription factor-binding motifs in the 0.7 kb promoter: CRE#2–E#1–CRE#1 in the proximal region and Mef2#3–CRE#3–E#4 in the distal region. Utilizing transcription assays, we have also shown that the reporter containing the Mef2#3–CRE#3–E#4 motifs is synergistically transactivated by Mef2c and Creb1. Further studies have mapped out the protein–protein interaction between Mef2c and Creb1. In summary, our present studies support the notion that the triple complex of Mef2c, Creb1 and Myod interacts with the Mef2#3–CRE#3–E#4 motifs in the distal region of the Tceal7 promoter, thereby driving Tceal7 expression during skeletal muscle development and regeneration.

We have previously reported Tceal7 as a muscle-specific gene that represses myoblast proliferation and promotes myogenic differentiation. The regulatory mechanism of Tceal7 gene expression has been well clarified recently. However, the underlying mechanism of Tceal7 function in skeletal muscle development remains to be elucidated. In the present study, we have generated an MCK 6.5 kb-HA-Tceal7 transgenic model. The transgenic mice are born normally, while they have displayed defects in the growth of body weight and skeletal muscle myofiber during postnatal development. Although four RxL motifs have been identified in the Tceal7 protein sequence, we have not detected any direct protein-protein interaction between Tceal7 and Cyclin A2, Cyclin B1, Cylin D1, or Cyclin E1. Further analysis has revealed the interaction between Tceal7 and Cdk1 instead of Cdk2, Cdk4, or Cdk6. Transgenic overexpression of Tceal7 reduces phosphorylation of 4E-BP1 Ser65, p70S6K1 Thr389, and Cdk substrates in skeletal muscle. In summary, these studies have revealed a novel mechanism of Tceal7 in skeletal muscle development.