The block of thyroglobulin synthesis, which occurs upon transformation of rat thyroid epithelial cells, is at the transcriptional level and it is associated with methylation of the 5' flanking region of the gene.

Transformation of rat thyroid epithelial cells by Kirsten murine sarcoma virus results in the block of certain thyroid differentiated functions, such as synthesis and secretion of thyroglobulin. Our studies, performed by a run-on assay, demonstrate that this block occurs at the transcriptional level. We also demonstrate the de novo methylation of two methylation-sensitive sites, located within the 5' end regulatory sequences of the thyroglobulin gene, in transformed cells, in the absence of any rearrangement of the gene. These two methylation-sensitive sites were methylated also in a rat thyroid cell line transformed by another retrovirus and in two normal cell lines which do not express the thyroglobulin gene.