Androgen Modulation of DNA-Binding Factors in the Mouse Kidney

Abstract

Transcription of the RP2 gene in the mouse kidney is induced by androgens. This induction is species specific within the genus Mus. For example, the gene responds to androgens in Mus domesticus, but is refractory to hormone in the distantly related species M. caroli. In the present report we have characterized DNA-binding factors that recognize the 5' flanking region of the RP2 gene. One factor (termed RPBF-1) binds a DNA fragment spanning the region between -157 and -311 relative to the transcriptional start site. RPBF-1 is present in kidney nuclear extracts from both control and androgen-treated M. domesticus as well as from control M. caroli; however, in the latter species a distinct factor (termed RPBF-2) is induced by androgens and replaces RPBF-1. The androgen-dependent replacement of RPBF-1 by RPBF-2 is specific to the kidney of M. caroli. DNase-1 footprinting analyses indicate that the two factors recognize distinct, yet overlapping, regions of the RP2 promoter: RPBF-1 binds the region between -247 and -269, while RPBF-2 binds the region between -265 and -290. The RPBF-2-binding site contains a sequence that is homologous to that recognized by nuclear factor-1 (NF-1), suggesting that RPBF-2 is a NF-1-like factor. This is supported by competition experiments with synthetic oligonucleotides corresponding to the NF-1-binding site within the adenovirus origin of replication. Thus, androgens can modulate, in a species- and tissue-specific manner, DNA-binding factors that recognize promoter regions of genes.(ABSTRACT TRUNCATED AT 250 WORDS)