TRANSCRIPTIONAL REGULATION BY STEROID-HORMONES

Steroid hormones influence the transcription of a large number of gene s by virtue of their interaction with intracellular receptors, which a re modular proteins composed of a ligand binding domain, a DNA binding domain, and several transactivation functions distributed along the m olecule. The DNA binding domain is organized around two zinc ions and allows the receptors to bind as homodimers to palindromic DNA sequence s, the hormone responsive elements (HRE), in such a way that each homo dimer contacts one half of the palindrome. Since the two halves are se parated by three base pairs, the two homodimers contact the same face of the double helix. Before hormone binding, the receptors are part of a complex with multiple chaperones which maintain the receptor in its steroid binding conformation. Following hormone binding, the complex dissociates and the receptors bind to HREs in chromatin. Regulation of gene expression by hormones involves an interaction of the DNA-bound receptors with other sequence-specific transcription factors and with the general transcription factors, which is partly mediated by co-acti vators and co-repressors. The specific array of cis regulatory element s in a particular promoter/enhancer region, as well as the organizatio n of the DNA sequences in nucleosomes, specifies the network of recept or interactions. Depending on the nature of these interactions, the fi nal outcome can be induction or repression of transcription. The vario us levels at which these interactions are modulated are discussed usin g as an example the promoter of the Mouse Mammary Tumor Virus and its organization in chromatin.