Pc. Supakar et al., A NOVEL REGULATORY ELEMENT ASSOCIATED WITH AGE-DEPENDENT EXPRESSION OF THE RAT ANDROGEN RECEPTOR GENE, The Journal of biological chemistry, 268(35), 1993, pp. 26400-26408
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.