Covalent modification and repressed transcription of a gene in hepatoma cells.

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Abstract
When liver cells undergo malignant transformation, certain genes cease being expressed. The structure of 1 such gene was studied. The protein product of this gene was designated hepatic protein 22 (hp22), which is not expressed in the 2 Morris hepatomas studied. A chimeric clone of pBR322 was prepared containing cDNA sequences complementary to mRNA coding for this protein. Using this cloned cDNA, changes in expression of this gene and changes in the restriction pattern of the DNA isolated from normal liver and these hepatomas were examined. In both hepatomas, studies using the isoschizomeric pair of restriction enzymes Msp I and Hpa II have indicated hypermethylation of a cytosine residue within or proximal to the hp22 gene. Other differences in the restriction pattern between normal liver and hepatoma DNA were detected with EcoRI and Ava I. In the nontranscribed form of this gene, the DNA has undergone covalent modification, distinguishing these 2 hepatomas from each other and from normal liver.