Determinants of target gene specificity for steroid/thyroid hormone receptors

doi:10.1016/0092-8674(89)90051-2

Cell

Volume 57, Issue 7, 30 June 1989, Pages 1139-1146

https://doi.org/10.1016/0092-8674(89)90051-2 Get rights and content

Abstract

The molecular specificity of the receptors for steroid and thyroid hormones is achieved by their selective interaction with DNA binding sites referred to as hormone response elements (HREs). HREs can differ in primary nucleotide sequence as well as in the spacing of their dyadic half-sites. The target gene specificity of the glucocorticoid receptor can be converted to that of the estrogen receptor by changing three amino acids clustered in the first zinc finger. Remarkably, a single Gly to Glu change in this region produces a receptor that recognizes both glucocorticoid and estrogen response elements. Further replacement of five amino acids in the stem of the second zinc finger transforms the specificity to that of the thyroid hormone receptor. These findings localize structural determinants required for discrimination of HRE sequence and half-site spacing, respectively, and suggest a simple pathway for the coevolution of receptor DNA binding domains and hormone-responsive gene networks.

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Cell

ArticleDeterminants of target gene specificity for steroid/thyroid hormone receptors

Abstract

Biochem. Biophys. Res. Commun.

Cell

Cell

Trends Genet.

Cell

Cell

Cell

Cell

Cell

Neuron

Cell

Cell

Molecular cloning of human and rat complementary DNA encoding androgen receptors

Science

Domains of the glucocorticoid receptor involved in specific and non-specific deoxyribonucleic acid binding, hormone activation, and transcriptional enhancement

Mol. Endocrinol.

Firefly luciferase gene: structure and expression in mammalian cells

Mol. Cell. Biol.

The steroid and thyroid hormone receptor superfamily

Science

The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain

Nature

Identification of a receptor for the morphogen retinoic acid

Nature

Spatial and temporal expression of the retinoic acid receptor in the regenerating amphibian limb

Nature

Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells

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Article
Determinants of target gene specificity for steroid/thyroid hormone receptors