Epigenetic activation of phenylalanine hydroxylase in mouse erythroleukemia cells by the cytoplast of rat hepatoma cells.

Abstract
Friend mouse erythroleukemia cells do not synthesize detectable levels of phenylalanine hydroxylase [phenylalanine 4-monooxygenase; L-phenylalanine, tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1] and are unable to grow in medium totally lacking tyrosine. These cells were fused with the cytoplasts of rat hepatoma cells that synthesize phenylalanine hydroxylase constitutively. Cytoplasmic hybrids [cybrids] were selected in medium without tyrosine. Cybrid clones expressed phenylalanine hydroxylase enzyme, which was of mouse type as determined by immunotitration and isoelectric focusing. This phenotype was maintained even in the absence of any selective pressure. In contrast, in whole cell hybrids derived between the same parents, the expression of the phenylalanine hydroxylase gene was totally extinguished. The cytoplasm of rat hepatoma cells may contain a positively acting factor(s) for the phenylalanine hydroxylase gene that brings about the activation of this gene in erythroleukemia cells.