Effects of DNA methylation on the altered structure of chromatin in thyroid disease

Abstract

Impaired regulation of thyroglobin (TG) gene expression is observed in various forms of thyroid pathology. The impairment in question can be explained by the transcription events that depend not only on the primary sequence of nucleotides in the DNA structure, but also on structural and functional alterations in the chromatin of thyroid cells. DNA methylation is the mechanism regulating TGgene transcription. It has a significant effect on the structure of DNA itself and on DNAase-sensitive sites, as well as on the interaction of DNA with various proteins including RNA polymerase.

In the context the yield of hydrolyzed DNA from the nuclei, DNAase I-hypersensitivity of methylated chromatin in the nuclei of thyroid cells was 10% while that of поп-methylated chromatin n isolated nuclei was 50%. In nodal euthyroid goiter, DNAase I-hypersensitivity of methylated chromatin was 7%> and that of nonmethylated one was 10%. In congenital goiter, the hypersensivity of поп-methylated chromatin in the isolated nuclei was 0.

An investigation of the RNA-polymerase activity of thyroid cellular nuclei under the influence of methylation indicated a substantial decrease in RNA synthesis irrespective of the type of an abnormality.