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mSharp-1/DEC2, a basic helix-loop-helix protein functions as a transcriptional repressor of E box activity and Stra13 expression.

Transcription factors belonging to the basic helix-loop-helix (bHLH) family play critical roles in the regulation of cellular differentiation of distinct cell types. In this study, we have characterized the DNA-binding and transcriptional properties of the bHLH factor mSharp-1/DEC2. mSharp-1 belongs to the Hairy/Enhancer of Split subfamily of bHLH factors and exhibits the highest structural and sequence identity with Stra13. We show that mSharp-1 specifically binds to the E box motif (CANNTG) as a homodimer and acts as a potent transcriptional repressor of MyoD- and E12-induced E box activity and differentiation. The inhibitory activity of mSharp-1 occurs through several mechanisms including occupancy of E box sites by mSharp-1 homodimers and by direct physical interaction with MyoD and E proteins. Furthermore, by using gel mobility shift assays and chromatin immunoprecipitation experiments, we have identified Stra13 as a target for mSharp-1-mediated repression. We demonstrate that transcriptional repression of Stra13 depends, in part, on binding of mSharp-1 to three conserved E box motifs in the Stra13 proximal promoter. Moreover, mSharp-1 directly interacts with the transcriptional activator Sp1 and impairs Sp1 induction of Stra13 promoter. Our results suggest that mSharp-1 functions as a transcriptional repressor by DNA binding dependent and independent mechanisms.

Pubmed ID: 12657651


  • Azmi S
  • Sun H
  • Ozog A
  • Taneja R


The Journal of biological chemistry

Publication Data

May 30, 2003

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • Electrophoretic Mobility Shift Assay
  • Helix-Loop-Helix Motifs
  • Homeodomain Proteins
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Repressor Proteins
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • Transcription, Genetic