Tse-2: a trans-dominant extinguisher of albumin gene expression in hepatoma hybrid cells.

Abstract

Serum albumin gene expression is generally extinguished in hepatoma x fibroblast hybrids. To define the genetic basis of this phenomenon, we screened a panel of hepatoma hybrids retaining different fibroblast chromosomes for albumin production by immunofluorescence. We report that albumin extinction in these clones was strictly correlated with the retention of mouse chromosome 1. Furthermore, albumin was systematically reexpressed in chromosome 1 segregants. These data define a tissue-specific extinguisher locus (Tse-2) that affects albumin gene expression in trans. Two other liver genes, those encoding liver alcohol dehydrogenase and liv-10, were coordinately extinguished with albumin in monochromosomal hybrids that specifically retained mouse chromosome 1.

Drosophila transcriptional repressor protein that binds specifically to negative control elements in fat body enhancers.

“…Negative regulatory elements have been identified in other tissue-specific enhancers (1,3,16,31,32,50,62,64). Of particular interest is the fact that many mammalian liver-specific genes, including the apolipoprotein Al gene (35), the tyrosine aminotransferase gene (8), the serum albumin gene, and the Adh gene (10), are under negative regulation. In these examples, it appears that negative regulatory proteins act to prevent the transcription of certain genes in inappropriate tissues.…”

Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes

“…This trans-dominant effect is mediated by a genetic locus designated tissue-specific extinguisher 1 (Tse-7) (Killary and Fournier, 1984). Another extinguisher locus (Tse-2) that maps to a different mouse chromosome (Petit et al, 1986;Chin and Fournier, 1989) selectively affects albumin and alcohol dehydrogenase.…”

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-Dependent protein kinase

“…Other extinguisher loci regulate expression of distinct sets of genes in hepatic cells, as all liver-specific traits are extinguished in karyotypically complete hepatoma x fibroblast hybrids (Chin and Fournier, 1987). For example, Tse-2 on mouse chromosome 1 represses expression of the serum albumin and alcohol dehydrogenase genes (Petit et al, 1986;Chin and Fournier, 1989).…”