Nuclear acceptor sites for sex steroid hormone receptors in chromatin.

The steroid receptor interactions in vitro with specific acceptor sites composed of acceptor protein-DNA complexes fulfill many of the criteria of a physiologically significant binding system. Chromatin acceptor sites for many steroid receptors (especially for the progesterone and estrogen receptor) are specific since they are saturable and competitive with unlabelled receptors, have high affinity for the receptor, distinguish between functional and nonfunctional receptors and demonstrate target tissue specificity. Pure DNA as acceptor sites does not display many of these properties. Therefore, it is clear that certain chromatin proteins provide the necessary specificity for the acceptor sites for the steroid receptors. For the progesterone receptor in the chick oviduct, these nuclear sites appear to contain specific chromosomal proteins as well as specific DNA sequences. The substitution of other chromosomal proteins or the genomic DNAs from evolutionarily distant organisms results in a loss of the specific nuclear binding. The nuclear acceptor sites appear to be resistant to the DNase activity which is not characteristic of transcriptionally active domains of the genome. Further studies using the ovalbumin gene sequences from genomic clones also indicate that none of the sequences within this domain and the 3-k flanking regions appear to contain the specific acceptor sequences. These observations have led to development of a model suggesting that the steroid receptors bind to acceptor sites distant from the structural genes the steroids ultimately regulate. Neighboring these acceptor sites are regulatory genes which code for regulatory substances which in turn (as secondary messengers) regulate at great distances the expression of the structural gene. This model might better fit the sex steroids which require 1-2 h to measurably alter gene transcription, as opposed to the glucocorticoids which more rapidly alter gene expression.