Increased Thermal Stability of Chromatin Containing 5-Bromodeoxyuridine-Substituted DNA

Abstract

The replacement of thymidine by 5-bromodeoxyuridine in DNA leads to a greatly enhanced stability of chromatin from hepatoma tissue culture or embryonic rat pancreas, as measured by thermal chromatography on hydroxylapatite. The increased stability is directly correlated with the degree of bromodeoxyuridine substitution. On the other hand, the incorporation of bromodeoxyuridine into DNA results in a modest stabilization of purified DNA. Substitution of nucleotide also alters slightly the hyperchromicity profile generated during the thermal denaturation of purified DNA and chromatin. The observed changes can best be explained by an altered interaction between the bromodeoxyuridine-DNA and other chromatin components, presumably proteins. These results suggests that the selective effects of bromodeoxyuridine on cytodifferentiation may be due to an increased affinity of regulatory proteins for bromodeoxyuridine-DNA.