Altered histone-DNA interactions in rat liver chromatin containing 5-bromodeoxyuridine-substituted DNA.

The extractability of the different histone types from rat liver chromatin was studied following the incorporation of bromodeoxyuridine (BrUdR) in liver DNA. This was accomplished by a continuous application of 20 mumol BrUdR/ml/h 17--41 after partial hepatectomy. As a result, thymidine (TdR) replacement by BrUdR of about 80% in the newly-synthesized DNA strand of approx. 30% of total liver DNA was obtained; this causes remarkable changes in the histone--DNA interactions as determined from the release of histones from liver nuclei by ammonium sulfate and ethidium bromide (EB), respectively. In particular, the relative amounts of the two slightly lysine-rich histones H2A and H2B remaining on the BrUdR chromatin proved to be about 3-fold higher than those remaining on the control chromatin of TdR-treated animals. Similarly, histones H1 and H3 tend to bind closer to BrUdR-containing DNA. These results may be of interst with regard to the well-known selective effects of BrUdR on differentiation processes.