Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive element

Abstract

Steroid hormone receptors activate specific gene transcription by binding as hormone-receptor complexes to DNA enhancer elements termed hormone responsive elements. A highly conserved 66-amino-acid region of the oestrogen and glucocorticoid receptors which corresponds to part of the receptor DNA-binding domain (region C) determines the specificity of target gene recognition. This region contains two subregions (CI and CII), encoded in two separate exons, that are analogous to the 'zinc fingers' of the transcription factor TFIIIA. The N-terminal CI finger determines the recognition specificity of the hormone responsive element. A chimaeric oestrogen receptor, in which the CI finger is replaced with the corresponding glucocorticoid receptor CI finger region, activates transcription from a reporter gene containing a glucocorticoid-responsive element, but not from a reporter gene containing an oestrogen-responsive element. We report here that three amino acids located at the C-terminal side of the oestrogen receptor CI finger play a key part in this specificity.

Regulation of prothymosin α by estrogen receptor α: molecular mechanisms and relevance in estrogen-mediated breast cell growth

“…No activation of the (7679/7637)-PTa CAT reporter construct was observed with expression vectors for ERa with mutations in the DNA binding domain and AF2 region (Figure 4). ERa with three mutations in the DNA binding domain (HE82) that converts DNA binding specificity from an ERE to Glucocorticoid Receptor Response Element (GRE) (Mader et al, 1989) did not induce enhancer activity. However deletion of the A/B domain, which has been shown to disrupt Activation Function 1 (AF-1) of the ER (Ali et al, 1993) did not significantly affect the ability of ERa to mediate activation of the PTa gene promoter reporter construct.…”

“…The expression vectors for the wild type human ERa (pCMV5-ER), ERa Activation function mutant ERa DA/B , ERa DNA binding mutant ER HE82 (E203G/G204S/A207V) which changes DNA binding specificity to a GRE, and ERa Activation Function 2 mutant ER AF2mut (L540Q/E542A/ D545A) have been described previously (LeGoff et al, 1994;Montano and Katzenellenbogen, 1997;Montano et al, 1996;Wrenn and Katzenellenbogen, 1993;Mader et al, 1989). The plasmid pCMVb (Clontech, Palo Alto, CA, USA) which encodes the b-galactosidase gene, was used as an internal control for transfection efficiency in all experiments.…”

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

“…There is a large degree of homology for the DNA binding domains of the hMR and hGR (> 90%, Arriza et al, 1987), but also for domains of other receptors belonging to the same superfamily. However, a certain degree of specificity is retained in the N-terminal zinc finger: For instance, three amino acid residues in this zinc finger are essential for the specificity of the DNA binding domain of the GR and the estrogen receptor (Green et al, 1988;Mader et al, 1989;Danielsen et al, 1989;Umesono and Evans, 1989). The N-terminal zinc finger binds to specific nucleotides of the hormone responsive element while the C-terminal zinc finger is more important for stabilization of the protein-DNA complex (Chalepakis et al, 1988;Hard et al, 1990;Luisi et al, 1991).…”

Estrogen and progesterone receptors in human papilloma virus-related cervical neoplasia

“…It is known that the upstream regulatory region of several HPVs contains glucocorticoidresponsive elements (5). These hormones have a receptor similar to that of the estrogen receptor (ER) hormone (5)(6)(7).…”