Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes.
Mice homozygous for deletions around the albino locus fail to activate expression of a set of neonatal liver functions and die shortly after birth. This phenotype is thought to result from the loss of a positive transacting factor, denoted alf, in deletion homozygotes. Using differential cDNA screening, we isolated and characterized genes whose cell type-specific transcription is affected by alf and found as a common feature that expression of these genes is induced by glucocorticoids and cAMP. Surprisingly, a subset of these alf-responsive genes is negatively controlled by the tissue-specific extinguisher locus Tse-1. Administration of glucocorticoids and cAMP leads to reversal of Tse-1-mediated extinction of these genes. These results show that two trans-acting factors coordinately regulate expression of overlapping sets of liver-specific genes. We suggest that both the lethal phenotype and the extinguished state result from interference with hormone signal transduction.
Ruppert
S
S
Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.
Boshart
M
M
Bosch
F X
FX
Schmid
W
W
Fournier
R E
RE
Schütz
G
G
D000818:Animals; D015152:Blotting, Northern; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*
D012333:RNA, Messenger; D015534:Trans-Activators