Regulatory Elements in Steroid Hormone Inducible Genes: Structure and Evolution of DNA Sequences Recognized by Steroid Hormone Receptors

Abstract

The mechanism by which steroid hormones control the synthesis of specific proteins in target cells has attracted the attention of molecular biologists because it represents a useful model system for studying regulation of gene expression in terminally differentiated cells of higher organisms. The cellular effects of steroid hormones are mediated by their corresponding receptors that, after binding the hormone, interact with specific sites in chromatin (1, 2). Considerable effort has been devoted to elucidate the mechanism of this interaction. Until recently a widespread hypothesis assumed the existence of specific “acceptor” sites in the chromatin of target cells, composed essentially of non-histone chromosomal proteins (3). This idea was based on the observation of a saturable preferential binding of hormone receptor to isolated nuclei or chromatin from target cells (4–8). However, some of these observations were later questioned, and they probably reflected in vitro artifacts (9–12). On the other side, a direct binding of hormone-receptor complexes to naked DNA has been observed in several systems (4, 12–14) and therefore the possibility was considered that the receptors could recognize specific DNA sequences (15, 16).