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Sequence-specific binding of androgen-receptor complexes to prostatic binding protein genes
F Claessens1, N K Rushmere, P Davies
1Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Belgium.
Molecular and Cellular Endocrinology
|December 21, 1990
Summary
Androgen receptor binding sites in rat prostatic binding protein genes may regulate gene expression. Researchers identified potential androgen response elements (AREs) but found varied functional activity, suggesting complex regulation.
Area of Science:
- Molecular Endocrinology
- Gene Regulation
- Prostate Biology
Background:
- Prostatic binding protein (PBP) is a glycoprotein complex (C1, C2, C3) crucial in the rat ventral prostate.
- Expression of PBP genes is regulated by androgens.
Purpose of the Study:
- To investigate the molecular mechanisms of androgenic control over PBP gene expression.
- To identify and characterize androgen response elements (AREs) in PBP genes.
Main Methods:
- Analysis of genomic fragments containing PBP genes and flanking sequences.
- Androgen receptor-DNA binding assays using mutated and synthetic sequences.
- Reporter gene assays to assess promoter activity.
Main Results:
- Androgen receptor-binding regions were identified upstream and within the first intron of PBP genes.
- Sequences resembling glucocorticoid response elements (GREs) were found, and mutations affected receptor binding.
- A consensus ARE sequence was proposed, but only one intronic fragment conferred significant androgen responsiveness in a heterologous promoter assay.
Conclusions:
- Direct androgen receptor-DNA interactions likely mediate androgenic control of PBP gene expression.
- Putative AREs were identified, but their functional significance varies, indicating complex regulatory mechanisms.
- Further investigation is needed to elucidate the intricate androgen regulation of PBP genes.