REGULATION OF GENE-EXPRESSION BY STEROID-HORMONES

The general model of activation of gene expression by steroid hormones is the conversion of the steroid hormone receptor from a nonDNA-binding complex into a DNA-binding protein. This chapter discusses the different elements that mediate the steroid hormone response. It also discusses different sequences that mediate a positive action of steroid hormones. Sequences that mediate a negative action of steroid hormones have also been classified into various mechanistic groups. Most of these cis-acting elements have been shown to bind the various steroid receptors by in vitro binding studies using “naked” DNA. However, in vivo, the receptor binding sites do not occur on naked DNA, but are nucleosomally packaged. There is, therefore, the major question of the way steroid hormone receptors recognize their cognate binding sites on chromatin to regulate transcription. Experiments with reconstituted chromatin on a short DNA from the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) show that the glucocorticoid receptors and the progesterone receptors bind naked DNA and reconstituted nucleosomes with equivalent affinity. However, nuclear factor I (NFI), a transcription factor essential for MMTV promoter activity, binds tightly to naked DNA, but not at all to the in vitro nucleosomally organized promoter. This has, therefore, led to the notion that hormone induction at the MMTV promoter proceeds through the displacement of a nucleosome at the hormone-response elements by the steroid receptors, allowing transcription factors, such as NFI, to bind to the promoter. © 1992 Academic Press, Inc.