The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors Academic Article uri icon

Overview

MeSH Major

  • Carrier Proteins
  • DNA-Binding Proteins
  • Receptors, Estrogen
  • Receptors, Thyroid Hormone
  • Regulatory Sequences, Nucleic Acid
  • Transcription, Genetic

abstract

  • Characterization of several thyroid hormone (T3), retinoic acid, and estrogen response elements has led to the identification of conserved DNA half-sites (core binding motifs). We present evidence that differences in both the relative orientation and spacing of these motifs within hormone response elements determine the distinct transcriptional responses of three members of the nuclear receptor superfamily. When separated by 3 bp, direct repeat, palindromic, and inverted palindromic arrangements of these motifs impart selective transcriptional responses to retinoic acid, estrogen, and T3 receptors, respectively. Varying the spacing between core motifs alters the specificity. Without spacing, a direct repeat of the core motif paradoxically configures the T3 receptor to confer transactivation in the absence of T3 and repression in its presence. Such an element occurs naturally in the mouse beta-thyrotropin promoter, physiologically under negative regulation by T3. The orientation and spacing of core binding motifs may thus function in concert as a code that accounts for the selective patterns of transcriptional responses of hormonally regulated promoters.

publication date

  • December 1991

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 1648451

Additional Document Info

start page

  • 1267

end page

  • 79

volume

  • 65

number

  • 7