Multiple components of a complex androgen-dependent enhancer.
Sex-limited protein (Slp) is expressed in adult male mice. A 160-basepair fragment 2 kilobases upstream of the gene serves as an androgen-dependent enhancer of chloramphenicol acetyltransferase expression in transient transfection assays in cells with endogenous or cotransfected androgen receptor. One element that is necessary, but not sufficient, for induction is a consensus glucocorticoid (or hormone) response element (HRE). This element binds to the mouse androgen receptor in vitro, but with apparent weak affinity. Induction by the HRE is greatly augmented by an accessory sequence within the 160 basepairs, suggesting that cooperative interactions confer strong response to androgen. Additional elements within the enhancer modulate induction, positively or negatively, and exhibit cell-specific behavior. Of particular interest are two degenerate HREs that are adjacent to the consensus sequence; they show no independent activity, but are functionally significant in conjunction with other elements. The complexity of this enhancer may reflect biological mechanisms that ensure specificity of hormonal response and allow gene expression to respond to changes in hormone concentration.
Adler
A J
AJ
Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0618.
Scheller
A
A
Hoffman
Y
Y
Robins
D M
DM
D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003181:Complement C4; D004268:DNA-Binding Proteins / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D008099:Liver / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection
D001798:Blood Proteins; C018386:C4a protein, mouse; D003181:Complement C4; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; D015500:Chloramphenicol O-Acetyltransferase