Ruppert, Siegfried; Boshart, Michael; Bosch, Franz X.; Schmidt, Walter; Fournier, R. E. Keith; Schlitz, Günther
Two Genetically Defined Tram-Acting Loci Coordinately Regulate Overlapping Sets of Liver-Specific Genes.
In: Cell, Vol. 61, No. 5: pp. 895-904
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 trans-acting 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.