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Nucleotide substitutions differentially affect direct repeat and palindromic thyroid hormone response elements

R W Katz1, R J Koenig

  • 1University of Michigan Medical Center, Ann Arbor 48109-0678.

The Journal of Biological Chemistry
|April 1, 1994
PubMed
Summary
This summary is machine-generated.

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Thyroid hormone receptors regulate gene expression. Palindromic elements require specific DNA sequences (TA) for function, unlike direct repeat elements, impacting gene regulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Thyroid hormone receptors (TRs) are ligand-dependent transcription factors.
  • TRs bind to thyroid hormone response elements (TREs) in DNA.
  • TREs can be direct repeats or palindromic arrangements of half-sites, traditionally AGGTCA.

Purpose of the Study:

  • To investigate the role of 5'-nucleotides in TRE function.
  • To determine if half-site sequence alterations affect direct repeat and palindromic TREs similarly.
  • To correlate DNA binding affinity with hormone induction levels.

Main Methods:

  • Analysis of gene expression from engineered TREs.
  • Comparison of palindromic and direct repeat TRE function.
  • Assessment of TR binding affinities in various configurations.

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Main Results:

  • Palindromic TREs exhibit high dependence on the 5'-TA sequence for function.
  • Direct repeat TREs show minimal influence from these 5'-nucleotides.
  • Hormone induction poorly correlates with monomer, homodimer, or heterodimer binding affinity.

Conclusions:

  • The orientation of half-sites and flanking sequences significantly impacts TRE function.
  • Palindromic TREs are uniquely sensitive to the 5'-TA motif.
  • Protein conformation, influenced by DNA sequence and orientation, may dictate hormone induction magnitude.