Sex-specific alterations in chromatin conformation of the brain of aging mouse.

Chromatin conformation has been analysed in the brain cortex of adult (24+/-2 weeks) and old (65+/-4 weeks) male and female mice. Nuclei purified from different groups of mice were digested with MNase and DNase I for varying time periods (0-90 min), and with endogenous endonucleases for 1 h. MNase and DNase I digestion kinetics showed that the percentage of acid solubility of chromatin was relatively lower in old than adult and in female than male. This was further supported by electrophoretic analysis of nuclease digested DNA fragments. When the nuclei were incubated with only Ca2+ or Mg2+, no endonuclease digestion was observed. However, under similar conditions, the liver DNA was cleaved substantially. When divalent cations were added together, they activated endogenous endonucleases and digested the brain chromatin. The activity of Ca2+/Mg2+-dependent endogenous endonucleases was higher in male than female. Thus the accessibility of chromatin to MNase, DNase I and endogenous endonucleases was higher in male than female, and MNase as well as DNase I were more active in adult than old. Such sex- and age-dependent conformation of chromatin may attribute to differential expression of genes in the mouse brain.