Receptors for glucocorticosteroid and progesterone recognize distinct features of a DNA regulatory element

Abstract

The chicken lysozyme gene can be induced in oviduct cells by four classes of steroid hormones, including glucocorticosteroids and progestins. The glucocorticosteroid receptor of rat liver and the progesterone receptor of rabbit uterus both bind, although with different relative affinities, to two sites in the promoter region of the chicken lysozyme gene located, respectively, between 50 and 80 and between 160 and 200 base pairs upstream of the transcription start point. Now we show that the purified progesterone binding unit of the chicken oviduct progesterone receptor (Mr 110,000, or so-called B subunit) generates a DNase I protection pattern ("footprint") in the promoter-distal site that is longer than the footprint generated by the glucocorticosteroid receptor. Methylation protection studies within the promoter-distal binding site identify four contact points for the chicken progesterone receptor and three contact points for the glucocorticosteroid receptor, of which only one is shared by both receptors. Computer graphics models allow one to envisage a different interaction of each receptor with the B form of the DNA double helix.