Identification and functional analysis of consensus androgen response elements in human prostate cancer cells.

Abstract

Androgen receptor (AR) recognizes and binds to 15-bp palindromic androgen response element (ARE) sequences with high affinity in vitro, which consist of two hexameric half-sites arranged as inverted repeats with a 3-bp spacer. Although a few near-consensus ARE sequences have been actually identified in the transcriptional regulatory regions of androgen-responsive genes, it has been unclear whether the exact consensus sequences function as bona fide AREs in vivo. A genome-wide in silico screening of palindromic AREs identified 563 exact consensus sequences in the human genome. The distribution of perfect palindromic AREs among the chromosomes is basically consistent with the length of chromosomes. Using human prostate cancer cell line LNCaP treated with a synthetic androgen R1881 as a model, in vivo AR binding abilities of 21 consensus AREs were analyzed by chromatin immunoprecipitation. Of 21 genomic fragments containing perfect AREs in chromosome X, 8 fragments recruited more ARs (>4-fold enrichment) even compared with the proximal ARE region of prostate-specific antigen. A couple of proximal genes or putative transcripts in the vicinity of the perfect AREs were found to be androgen-responsive analyzed by quantitative RT-PCR. Our results suggest that some of perfect palindromic AREs could function as in vivo AR binding sites in the human genome and regulate gene transcription.

• Authors: Kuniko Horie-Inoue, Hidemasa Bono, Yasushi Okazaki, Satoshi Inoue
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 325 Issue 4 Pg. 1312-7 (Dec 24 2004) ISSN: 0006-291X [Print] United States
• PMID: 15555570 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Receptors, Androgen

Topics

• Androgens (genetics, metabolism)
• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Chromosome Mapping
• Consensus Sequence (physiology)
• Humans
• Male
• Prostatic Neoplasms (genetics, metabolism)
• Receptors, Androgen (genetics, metabolism)
• Response Elements (genetics)
• Sequence Analysis, DNA (methods)