Mechanisms of polyanion stimulation of nuclear DNA synthesis: Examination of thermal destabilization

Abstract

The polyanions heparin and poly- l-glutamic acid stimulate endogenous DNA synthesis in isolated nuclei and chromatin and destabilize the 78000 g fraction of rat liver chromatin to thermal denaturation; however, there is a poor correlation between the polyanion concentrations that result in large-scale template destabilization and those that stimulate endogenous DNA synthesis. We have isolated a chromatin fraction that is enriched in endogenous DNA synthesis, the degree of enrichment being significantly greater with heparin-treated chromatin; however, in both treated and untreated chromatin this fraction is indistinguishable from the remaining chromatin by thermal denaturation in dilute EDTA. This fact, as well as the different polyanion concentrations required to alter endogenous DNA synthesis and thermal stability, leads us to conclude that large-scale template destabilization does not correlate with increased endogenous DNA synthesis.