Major chromatin changes accompany extinction of alpha-fetoprotein gene in hepatoma x fibroblast hybrids.

The sensitivity of the alpha-fetoprotein (AFP) gene to digestion by the enzyme DNaseI, and the presence of hypersensitive sites in the 5' region of this gene, were examined in hepatoma x fibroblast hybrid cells that exhibit extinction of AFP gene expression. Major changes occur in the extinguished gene, i.e., loss of long-range sensitivity to DNase digestion and of the hypersensitive sites. In this respect, the extinguished gene resembles the corresponding silent gene present in fibroblasts, but differs from the silent gene present in normal adult hepatocytes. These observations suggest that extinguisher factors acting on the AFP gene alter its conformation.