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Related Experiment Videos

Muscle specificity encoded by specific serum response factor-binding sites.

P S Chang1, L Li, J McAnally

  • 1Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9148, USA.

The Journal of Biological Chemistry
|March 30, 2001
PubMed
Summary

Flanking sequences near CArG boxes determine gene expression specificity. Variations in these sequences enable Serum Response Factor (SRF) to regulate both muscle-specific and growth factor-inducible genes.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Serum Response Factor (SRF) is a transcription factor regulating muscle-specific and growth factor-inducible genes via CArG boxes.
  • SRF expression alone does not explain the muscle specificity of all its target genes.

Purpose of the Study:

  • To investigate the role of SRF in muscle-specific transcription.
  • To determine how CArG box flanking sequences influence gene expression specificity.

Main Methods:

  • Created transgenic mice with lacZ reporter genes linked to various CArG boxes and flanking sequences.
  • Analyzed expression patterns in developing embryos.
  • Performed systematic swapping of core and flanking sequences.

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Main Results:

  • CArG boxes from SM22 and skeletal alpha-actin promoters directed muscle-restricted expression.
  • The c-fos CArG box directed widespread embryonic expression.
  • Flanking sequences, not the core CArG box, largely dictated cell type specificity.
  • Widespread expression sequences bound SRF more strongly than muscle-restricted sequences.

Conclusions:

  • Sequence variations in flanking regions of CArG boxes influence gene expression specificity.
  • These variations contribute to SRF's ability to differentiate between muscle-specific and growth factor-inducible genes in vivo.