Intronic androgen response elements of prostatic binding protein genes

Area of Science:

• Molecular Endocrinology
• Gene Regulation
• Prostate Cancer Research

Background:

• Prostatic Binding Protein (PBP) gene transcription is regulated by androgens.
• Androgen receptor (AR) binding regions are known to exist upstream and within introns of PBP genes.

Purpose of the Study:

• To precisely map the androgen receptor dimer binding site within the first intron of PBP genes.
• To identify functional androgen response elements (AREs) in these genes.
• To investigate the role of binding affinity in ARE function.

Main Methods:

• DNA-cellulose competition assays to identify AR-binding regions.
• DNase I footprinting assays to determine exact in vitro receptor dimer binding sites.
• Gene transfer experiments using chimeric gene constructs to assess functional AREs.

Main Results:

• The exact in vitro binding site for an androgen receptor dimer was identified in the first intron of the C3(1), C3(2), and C1 PBP genes.
• Functional androgen response elements were confirmed in the C3 genes.
• The C1 intronic binding site exhibited significantly weaker affinity for the androgen receptor DNA-binding domain compared to C3 genes.

Conclusions:

• Specific androgen receptor dimer binding sites are located in the first intron of PBP genes.
• The identified binding sites in C3 genes function as androgen response elements.
• The weaker binding affinity of the C1 intronic site likely explains its lack of function as an androgen response element.