Determinants of target gene specificity for steroid/thyroid hormone receptors
- 1 June 1989
- journal article
- Published by Elsevier BV in Cell
- Vol. 57 (7), 1139-1146
- https://doi.org/10.1016/0092-8674(89)90051-2
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.Keywords
This publication has 38 references indexed in Scilit:
- Spatial and temporal expression of the retinoic acid receptor in the regenerating amphibian limbNature, 1989
- Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirpsNature, 1988
- Nuclear receptors enhance our understanding of transcription regulationTrends in Genetics, 1988
- Identification of a new member of the steroid receptor super-family by cloning and sequence analysisBiochemical and Biophysical Research Communications, 1988
- Identification of a receptor for the morphogen retinoic acidNature, 1987
- A human retinoic acid receptor which belongs to the family of nuclear receptorsNature, 1987
- Oestrogen and glucocorticoid responsive elements are closely related but distinctNature, 1987
- Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptorCell, 1987
- Promoter Region of the Human Harvey ras Proto-Oncogene: Similarity to the EGF Receptor Proto-Oncogene PromoterScience, 1985
- STEROID RECEPTOR REGULATED TRANSCRIPTION OF SPECIFIC GENES AND GENE NETWORKSAnnual Review of Genetics, 1985