Effects of oestradiol on covalent modifications of chromosomal proteins and transcription of chromatin of the brain of rats of various ages

Abstract

In vitro phosphorylation, acetylation and methylation of histones and nonhistone chromosomal proteins (NHCP) and their modulation by oestradiol were studied in the cerebral cortex of female rats of different ages. All the three modifications of histones are highest in immature rats. Phosphorylation and acetylation of histones decrease with age, but methylation is higher in the old than in the adult. NHCP show an age-dependent increase in phosphorylation, but a decrease in acetylation and methylation. Phosphorylation of H1 and H4, and acetylation of H3, H4, H2A and H2B decreases with age. H3 and H4 methylation is highest in the immature and decreases with age. Modifications of only a few NHCP change as a function of age. Oestradiol stimulates phosphorylation of total histones and NHCP of immature and adult rats, but has no significant effect in old age. Acetylation of histones and NHCP of immature rats is stimulated by the hormone. Nuclei were purified from tissues after acetylation with and without 17β-oestradiol and incubated with [³H]-UTP. Transcription was significantly higher after oestradiol treatment Oestradiol stimulates methylation of chromosomal proteins of the adult only. Thus, alterations in covalent modifications of chromosomal proteins and their specific modulation by oestradiol may cause differential expression of genes and influence the aging process.