Transcription Regulation of Tceal7 by the Triple Complex of Mef2c, Creb1 and Myod

SIMPLE SUMMARY: We have previously reported a striated muscle-specific gene during embryogenesis, Tceal7. Our studies have characterized the 0.7 kb promoter of the Tceal7 gene, which harbors important E-box motifs driving the LacZ reporter in the myogenic lineage. However, the underlying mechanism regulating the dynamic expression of Tceal7 during skeletal muscle regeneration is still elusive. In the present work, we have defined a cluster of Mef2#3–CRE#3–E#4 motifs through bioinformatic analysis and transcription assays. Our studies suggested that the triple complex of Mef2c, Creb1 and Myod binds to the Mef2#3–CRE#3–E#4 cluster region, therefore driving the dynamic expression of Tceal7 during skeletal muscle regeneration. The novel mechanism may throw new light on understanding transcription regulation in skeletal muscle myogenesis. ABSTRACT: 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.