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 has co-evolved with the sexual mode of reproduction (Partridge, L., and Barton, N. H. (1993) Nature 362, 305-311). Age-dependent changes in target cell sensitivity to reproductive hormones can be considered part of this evolutionary linkage. Here we describe a novel regulatory element in the rat androgen receptor (AR) gene promoter associated with its 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). Both deletion and point mutations of the ADF site result in about a 5-fold decline in the AR promoter function. Unlike AF, which is relatively tissue specific, ADF appears to be ubiquitous. The ubiquitous and evolutionarily conserved nature of ADF suggests a fundamental role of this novel transcription factor in programmed gene expression.
Supakar
P C
PC
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Song
C S
CS
Jung
M H
MH
Slomczynska
M A
MA
Kim
J M
JM
Vellanoweth
R L
RL
Chatterjee
B
B
Roy
A K
AK
D000375:Aging / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D017124:Conserved Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011944:Receptors, Androgen / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D011944:Receptors, Androgen