DNA regulatory elements for steroid hormones

Abstract

Gene regulation by steroid hormones is mediated through an interaction of the hormone receptors with DNA regulatory sequences called hormone regulatory or responsive elements (HRE). An analysis of the HRE's in the DNA of mouse mammary tumour provirus, human metallothionein IIA gene, chicken lysozyme gene, chicken and Xenopus vitellogenin genes, growth hormones genes, Moloney murine sarcoma provirus, rabbit uteroglobin gene, rat tyrosine aminotransferase gene, rat tryptophan oxygenase gene and rat acidic glycoprotein gene, yields the following consensus for positively modulated glucocorticoid responsive elements (GRE): 5'-GGTACAnnnTGTTCT-3'. This element can also mediate induction by progesterone and probably by androgens, but not by estrogens. Detailed analysis of the DNA protection pattern suggests that a dimer of the hormone receptor interacts with this palindromic 15-mer. In genes that are negatively regulated by glucocorticoids an imperfect copy of the GRE is found, and repression is probably due to competition between hormone receptor and other transcription factors or enhancer binding proteins for binding to overlapping DNA sequences. The receptors without bound hormone are able to interact specifically with DNA in vitro, but binding of hormone is needed for transcriptional activation in vivo. This could be due, at least in part, to changes in the rate parameters of the receptor-DNA interaction induced by binding of the hormone to the receptor. The possible role of precise chromatin organization in glucocorticoid induction is discussed on the basis of the nucleosome phasing found in the LTR region of mouse mammary tumour virus.