title: Negative androgen-response elements mediate androgen-dependent transcriptional inhibition of TGF-β1 and CDK2 promoters in the prostate gland.
abstract: The androgen receptor (AR) is a ligand-dependent transcription factor that  mediates androgen functions by regulating the expression of genes it targets.  In the present study, we mapped 2 regions in human transforming growth factor  β1 and cyclin-dependent kinase 2 promoters that negatively regulated  transcriptional activity in an androgen-dependent manner in close proximity to  positive androgen-response elements (pARE). We identified 7 negative  androgen-response elements (nARE) in the negative androgen-response region in  the TGF-β1 promoter. Each nARE is composed of 15 nucleotides and mediates  androgen-dependent inhibition of transcription in close proximity of pAREs.  The 5' portions of nAREs are highly conserved and resemble core half  sites in pAREs. The nAREs interacted weakly with AR DNA-binding domain (AR  DBD) in gel shift assays. Mutations on the conserved nucleotides in the nARE  abolished its interaction with the AR DBD and abolished its inhibition of  androgen-driven transcription, suggesting that nARE/AR interaction is  essential for nARE-mediated inhibition of transcription. Taken together, these  findings indicate that the AR negatively regulates the expression of its  target genes via a negative androgen-response region composed of multiple  nAREs.
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Chu
authors.forename: Liran
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000728:Androgens / Q000502:physiology*; D001483:Base Sequence; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D000728:Androgens; D017931:DNA Primers; D053773:Transforming Growth Factor beta1; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2