Tissue-specific expression of the rat albumin gene: genetic control of its extinction in microcell hybrids

Numerous studies of cell hybrids have indicated that somatic cells produce negative regulators (extinguishers) that prevent the expression of functions foreign to their own differentiation. Here, we report genetic evidence of such control. In microcell hybrids between well-differentiated rat hepatoma cells and microcells of mouse fibroblast L cells, the extinction of albumin synthesis is directly related to the presence of a single specific chromosome of the mouse fibroblast parent. The expression of several other hepatic functions is not affected. Transfection of these hybrids with a recombinant plasmid, containing a tissue-specific control element of the upstream region of the rat albumin gene linked to coding sequences of the chloramphenicol acetyltransferase gene, reveals that extinction acts on or via this cis-control element.