Identification and characterization of a novel androgen response element composed of a direct repeat.
Transcriptional regulation by the androgen receptor (AR) requires its binding to hormone response element nucleotide sequences in DNA. A consensus glucocorticoid response element (GRE) can mediate transactivation by AR and other members of the AR/glucocorticoid (GR)/progesterone (PR)/mineralocorticoid (MR) receptor subfamily. We identified putative androgen response element (ARE) sequences by binding of a human AR DNA-binding domain fusion protein to DNA in a random sequence selection assay. A 17-base pair consensus nucleotide sequence, termed IDR17, containing three potential GRE-like core binding sites organized as both inverted and direct repeats, was determined from a pool of degenerate oligonucleotides. IDR17 was active in mediating androgen-dependent induction of reporter gene expression in transient transfection assays. Dissection of the IDR17 sequence revealed an 11-base pair sequence (DR-1), consisting of two potential core binding sites oriented as an overlapping direct repeat, as the most potent ARE. DR-1 demonstrated a strong preference for AR binding and transactivation when compared with GR. To our knowledge, this is the first observation that a direct repeat of GRE-like core motifs functions as a preferred hormone response element within the AR/GR/PR/MR subfamily of nuclear receptors.
Zhou
Z
Z
Department of Population Dynamics, Division of Reproductive Biology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Corden
J L
JL
Brown
T R
TR
D001483:Base Sequence; D001665:Binding Sites; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D005938:Glucocorticoids; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase