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DNA regulatory elements for steroid hormones.

M Beato1, G Chalepakis, M Schauer

  • 1Institut für Molekularbiologie und Tumorforschung, Philipps Universität, Marburg, F.R.G.

Journal of Steroid Biochemistry
|May 1, 1989
PubMed
Summary
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Steroid hormone receptors bind to DNA regulatory sequences called hormone responsive elements (HREs). A consensus glucocorticoid responsive element (GRE) sequence was identified, mediating gene regulation by multiple steroid hormones.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Steroid hormone action involves hormone receptors interacting with specific DNA sequences (HREs).
  • Understanding these interactions is crucial for deciphering gene regulation by hormones.

Purpose of the Study:

  • To identify and characterize consensus DNA sequences involved in steroid hormone receptor binding.
  • To elucidate the mechanism of gene regulation by glucocorticoids, including positive and negative modulation.

Main Methods:

  • Sequence analysis of HREs from various genes (e.g., mouse mammary tumour virus, human metallothionein IIA, chicken lysozyme).
  • DNA protection assays to study hormone receptor-DNA interactions.
  • In vitro and in vivo studies on receptor-DNA binding and transcriptional activation.

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Main Results:

  • A consensus sequence for positively regulated glucocorticoid responsive elements (GREs) was determined: 5'-GGTACAnnnTGTTCT-3'.
  • This GRE mediates induction by progesterone and androgens, but not estrogens.
  • Receptor dimerization and hormone binding are critical for transcriptional activation in vivo.

Conclusions:

  • The identified GRE sequence is a key regulatory element for multiple steroid hormones.
  • Negative regulation involves competition for binding sites, while hormone binding modulates receptor-DNA interaction kinetics.
  • Chromatin organization may play a role in glucocorticoid-induced gene expression.