Demethylation of the type I procollagen genes in transformed fibroblasts treated with 5-azacytidine.

Transformation of the human embryonic lung fibroblast line, WI-38, with simian virus 40 (SV40) results in inactivation of the type I procollagen genes. No type I collagen or procollagen mRNA is detected in these transformed cells, as determined by polyacrylamide gel electrophoresis. Analysis of the methylation patterns of these genes showed the type I procollagen genes to be hypermethylated at certain cytosine residues in the transformed cells. However, several of the cytosine residues were methylated in the normal cells where these genes are expressed. These methylation patterns can be altered by treatment of the cells with 5-azacytidine or 5-azadeoxycytidine, but without a resultant activation of the type I procollagen genes. These results show that demethylation alone is not sufficient for gene activation, but that other signals are also required.