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Related Experiment Videos

The Pan basic helix-loop-helix proteins are required for insulin gene expression

C A Vierra1, C Nelson

  • 1Department of Biochemistry University of California at Riverside 92521, USA.

Molecular Endocrinology (Baltimore, Md.)
|January 1, 1995
PubMed
Summary

Pan proteins are crucial for regulating rat insulin I gene transcription in pancreatic beta-cells. Inhibiting Pan protein synthesis via antisense transcripts significantly reduces insulin gene expression and enhancer activity.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • The rat insulin I gene enhancer has Nir and Far motifs, targeted by DNA-binding proteins for selective transcription in beta-cells.
  • Several helix-loop-helix (HLH) proteins bind these motifs in vitro, but their specific roles in vivo are unclear.

Purpose of the Study:

  • To investigate the specific role of Pan proteins in the transcriptional regulation of the rat insulin I gene.

Main Methods:

  • Created stable beta-cell integrants expressing Pan antisense transcripts to inhibit Pan protein synthesis.
  • Assessed the impact of diminished Pan protein levels on rat insulin gene transcription and Nir/Far element-binding activity.

Main Results:

  • Reduced Pan protein levels in beta-cells led to a significant decrease in rat insulin gene transcription.

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  • Lowered Pan protein expression correlated with reduced binding activity at the beta-endocrine-specific Nir and Far elements.

    • Conclusions:

    • Pan proteins are essential for active transcriptional regulation of the rat insulin I gene.
    • Pan proteins mediate their function by influencing the binding activity at the Nir and Far enhancer motifs in pancreatic beta-cells.