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Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C

J D Molkentin1, B L Black, J F Martin

  • 1Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas 75235, USA.

Molecular and Cellular Biology
|June 1, 1996
PubMed

Insights

Myocyte enhancer factor 2 (MEF2) proteins regulate muscle gene expression. Specific domains control DNA binding and activation, with some mutants inhibiting gene activation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • The myocyte enhancer factor 2 (MEF2) family comprises four transcription factors (MEF2A-D) crucial for muscle gene expression.
  • MEF2 factors bind DNA as dimers to activate transcription of muscle-specific genes.

Purpose of the Study:

  • To elucidate the functional mechanisms of MEF2 transcription factors in muscle gene activation.
  • To identify specific domains and amino acids responsible for MEF2 DNA binding, dimerization, and transcriptional activation.

Main Methods:

  • Generation of deletion and site-directed mutants of the MEF2C transcription factor.
  • Analysis of mutant MEF2C proteins to determine their effects on DNA binding, dimerization, and transcriptional activity.

Main Results:

  • The MADS and MEF2 domains are essential for DNA binding and dimerization.
  • The carboxyl terminus of MEF2C is required for transcriptional activation.
  • Specific amino acids within the MEF2 domain are critical for MEF2 site-dependent transcription, independent of DNA binding.
  • MEF2 mutants lacking DNA binding ability function as dominant negatives, inhibiting wild-type MEF2C activity.

Conclusions:

  • MEF2 transcription factors possess distinct domains for DNA binding, dimerization, and transcriptional activation.
  • The MEF2 domain plays a dual role in DNA binding and facilitating activation via interaction with the activation domain.
  • Understanding MEF2 mutant functions provides insights into the regulation of muscle gene expression.

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