Decreased Hnf-1 gene expression in mice homozygous for a 1.2-centiMorgan deletion on chromosome 7.
The mammalian CYP2E1 gene encodes a cytochrome P450 enzyme that is markedly increased soon after birth. In vitro evidence suggests that the rat CYP2E1 gene is positively regulated by the transcription factor HNF-1 or a protein displaying DNA-binding properties similar to HNF-1. In contrast to newborn wild-type mice and mice heterozygous for a 1.2-centiMorgan deletion on chromosome 7, newborn mice homozygous for this deletion do not show significant expression of the Cyp2e-1 and Hnf-1 genes. However, the Cyp2e-1 and Hnf-1 structural genes are not in the chromosome 7 segment deleted in these mice. Although Cyp2e-1 maps to chromosome 7, it is distal to this deletion; Hnf-1 maps to chromosome 5. These data suggest that the deleted region of chromosome 7 contains a gene encoding a trans-acting factor which is upstream (epistatic) in the regulatory cascade that includes Hnf-1 gene expression.
Gonzalez
F J
FJ
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Liu
S Y
SY
Kozak
C A
CA
Nebert
D W
DW
D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D006720:Homozygote; D006801:Humans; D051379:Mice; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015534:Trans-Activators; D014158:Transcription, Genetic
D012333:RNA, Messenger; D015534:Trans-Activators; D004247:DNA; D003577:Cytochrome P-450 Enzyme System