Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation

Xiaozhong Shi, Daniel J. Garry

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Recurrent injuries eventually exhaust the capacity of skeletal muscle to fully restore or regenerate its cellular architecture. Therefore a comprehensive understanding of the muscle regeneration programme is needed to provide a platform for new therapies for devastating diseases such as Duchenne muscular dystrophy. To begin to decipher the molecular programme that directs muscle regeneration, we undertook an unbiased strategy using microarray analysis of cardiotoxin-injured skeletal muscle at defined time periods in the adult mouse. Using this strategy, we identified Tceal7 [transcription elongation factor A (SII)-like 7], which was dynamically regulated during muscle regeneration. Our studies revealed that Tceal7 was restricted to the skeletal muscle lineage during embryogenesis. Using transgenic technologies and transcriptional assays, we defined an upstream 0.7 kb fragment of the Tceal7 gene that directed the LacZ reporter to the developing skeletal muscle lineage. Analysis of the Tceal7 promoter revealed evolutionarily conserved E-box motifs within the 0.7 kb upstream fragment that were essential for promoter activity, as mutation of the E-box motifs resulted in the loss of reporter expression in the somites of transgenic embryos. Furthermore, we demonstrated that MRFs (myogenic regulatory factors) were Tceal7 upstream transactivators using transcriptional assays, EMSAs (electrophoretic mobility-shift assays), and ChIP (chromatin immunoprecipitation) assays. Overexpression of Tceal7 in C2C12 myoblasts decreased cellular proliferation and enhanced differentiation. Further studies revealed that p27 expression was up-regulated following Tceal7 overexpression. These studies support the hypothesis that MRFs transactivate Tceal7 gene expression and promote muscle differentiation during muscle development and regeneration.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalBiochemical Journal
Volume428
Issue number2
DOIs
StatePublished - Jun 1 2010

Keywords

  • Muscle differentiation
  • Myogenic regulatory factor
  • Transcription elongation factor A (SII)-like 7 (Tceal7)

Fingerprint Dive into the research topics of 'Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation'. Together they form a unique fingerprint.

Cite this