Nuclear acceptor sites for steroid hormone receptors: comparisons of steroids and antisteroids.
The respective chromatin binding sites (acceptor sites) for both the avian oviduct progesterone receptor (PR) and the rabbit uterine estrogen receptor (ER) reported by two separate laboratories are compared. Support for a saturable, high affinity binding to the chromatin acceptor sites by both receptors is described. Nonradiolabelled PR or ER compete with their homologous radiolabelled receptors for binding. However, there is no competition between the heterologous ER and PR for the nuclear binding sites. In both receptor systems, evidence for a receptor dependent, receptor specific binding, which mimics the binding measured in vivo, is reported. With both the PR and ER, evidence for extensive masking in chromatin of many of the acceptor sites is described. The PR and ER acceptor sites appear to be composed of specific acceptor proteins bound to DNA. The dissociation of these proteins from DNA causes a loss of specific binding. Reannealing of these same chromatin protein fractions, but not other protein fractions, back to the DNA reinstates the specific PR binding. Antibodies against the PR acceptors proteins are described. These antibodies block PR but not ER binding to the chromatin acceptor sites, supporting the steroid receptor specific acceptor sites. In the rabbit uterine system, the ER acceptor proteins dissociate from chromatin in three distinct fractions according to their affinity for the DNA. Each of these fractions contains acceptor activity in that each can be reannealed to the DNA to reconstitute specific ER binding sites, i.e. those which are saturable, high affinity, and receptor dependent. Interestingly, the antiestrogen receptor complexes do not bind to one fraction of acceptor proteins which does bind the native estrogen receptor complex. This ER acceptor protein fraction contains two regions of acceptor activity in the molecular mass range of 50,000 and 12,000 daltons. The latter species is in the size range of the PR acceptor proteins. This difference in binding to chromatin acceptor sites by the estrogen receptor, complexed with an estrogen or antiestrogen, may explain the differential regulation of gene expression and the differential biological response to antiestrogens compared to the native estrogens.
Spelsberg
T C
TC
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN.
Ruh
T
T
Ruh
M
M
Goldberger
A
A
Horton
M
M
Hora
J
J
Singh
R
R
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D002843:Chromatin / Q000502:physiology; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D009687:Nuclear Proteins / Q000502:physiology; D009698:Nucleoproteins / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology*; D013256:Steroids / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014158:Transcription, Genetic
D002843:Chromatin; D009687:Nuclear Proteins; D009698:Nucleoproteins; D011987:Receptors, Steroid; D013256:Steroids