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Cell- and Gene-specific Regulation of Primary Target Genes by the Androgen Receptor

Overview
Journal Genes Dev
Specialty Molecular Biology
Date 2007 Aug 19
PMID 17699749
Citations 190
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Abstract

The androgen receptor (AR) mediates the physiologic and pathophysiologic effects of androgens including sexual differentiation, prostate development, and cancer progression by binding to genomic androgen response elements (AREs), which influence transcription of AR target genes. The composition and context of AREs differ between genes, thus enabling AR to confer multiple regulatory functions within a single nucleus. We used expression profiling of an immortalized human prostate epithelial cell line to identify 205 androgen-responsive genes (ARGs), most of them novel. In addition, we performed chromatin immunoprecipitation to identify 524 AR binding regions and validated in reporter assays the ARE activities of several such regions. Interestingly, 67% of our AREs resided within approximately 50 kb of the transcription start sites of 84% of our ARGs. Indeed, most ARGs were associated with two or more AREs, and ARGs were sometimes themselves linked in gene clusters containing up to 13 AREs and 12 ARGs. AREs appeared typically to be composite elements, containing AR binding sequences adjacent to binding motifs for other transcriptional regulators. Functionally, ARGs were commonly involved in prostate cell proliferation, communication, differentiation, and possibly cancer progression. Our results provide new insights into cell- and gene-specific mechanisms of transcriptional regulation of androgen-responsive gene networks.

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References
1.
Chang C, Kokontis J, Liao S . Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988; 240(4850):324-6. DOI: 10.1126/science.3353726. View

2.
Lehto M, Olkkonen V . The OSBP-related proteins: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signalling. Biochim Biophys Acta. 2003; 1631(1):1-11. DOI: 10.1016/s1388-1981(02)00364-5. View

3.
DiLeone R, Marcus G, Johnson M, Kingsley D . Efficient studies of long-distance Bmp5 gene regulation using bacterial artificial chromosomes. Proc Natl Acad Sci U S A. 2000; 97(4):1612-7. PMC: 26483. DOI: 10.1073/pnas.97.4.1612. View

4.
Bussemaker H, Li H, Siggia E . Building a dictionary for genomes: identification of presumptive regulatory sites by statistical analysis. Proc Natl Acad Sci U S A. 2000; 97(18):10096-100. PMC: 27717. DOI: 10.1073/pnas.180265397. View

5.
Rennie P, Bruchovsky N, Leco K, Sheppard P, McQueen S, Cheng H . Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene. Mol Endocrinol. 1993; 7(1):23-36. DOI: 10.1210/mend.7.1.8446105. View