Undermethylation at the 5' end of the albumin gene is necessary but not sufficient for albumin production by rat hepatoma cells in culture.

We have measured methylation of the albumin gene in clones of rat hepatoma cells that vary quantitatively in their rates of synthesis of albumin and in variant and hybrid cells that produce no albumin. Although the albumin gene is undermethylated for its entire length in rat liver, only the 5' end is ever undermethylated in hepatoma cells. Moreover, undermethylation of the 5' end of the gene appears to be necessary for stable expression of the albumin gene in hepatoma cells. Since undermethylation of this region is found in some variant cells that fail to produce albumin, it is not a sufficient condition for albumin gene expression. Despite the excellent correlation between undermethylation of the 5' end of the albumin gene and its stable expression, the results argue against the possibility that the methylated state of such genes during development determines whether they will or will not be expressed.