A NOVEL REGULATORY ELEMENT ASSOCIATED WITH AGE-DEPENDENT EXPRESSION OF THE RAT ANDROGEN RECEPTOR GENE

A large body of evidence indicates that the genetic program of aging h as co-evolved with the sexual mode of reproduction (Partridge, L., and Barton, N. H. (1993) Nature 362, 305-311). Age-dependent changes in t arget cell sensitivity to reproductive hormones can be considered part of this evolutionary linkage. Here we describe a novel regulatory ele ment in the rat androgen receptor (AR) gene promoter associated with i ts age-dependent expression in the liver. This element consists of two (19 and 25 base pairs) contiguous sites, one specifically binding an Age-dependent Factor (ADF) and the other an Associated Factor (AF). Bo th deletion and point mutations of the ADF site result in about a 5-fo ld decline in the AR promoter function. Unlike AF, which is relatively tissue specific, ADF appears to be ubiquitous. The ubiquitous and evo lutionarily conserved nature of ADF suggests a fundamental role of thi s novel transcription factor in programmed gene expression.