Increased acetylation of histones at an early stage of oestradiol-mediated gene activation in the liver of immature chicks.

The vitellogenin system of chicken was used to examine alterations in the microheterogeneity of chromosomal proteins in the course of steroid hormone-mediated gene expression. After administration of oestradiol-17 beta there is a dramatic increase in the number of copies of vitellogenin m-RNA in the liver of male oviparous animals, like Xenopus and chicken. According to earlier reports the rapid increase in transcriptional activity starts after a lag of 4 h. The system has also been examined as to the number of DNase I hypersensitive sites which appear to correlate with the degree of differentiation and hormonal activation. The time course of [3H]acetate incorporation into the histone fraction was monitored and the microheterogeneity of histones analysed by acid-Triton-urea gel electrophoresis. The results show that there is an increased degree of acetylation of histones in the liver of immature chicks as a result of oestradiol-17 beta administration. The change in the modification pattern of histones was found to be an early event, correlated with the time course of appearance of new DNase I hypersensitive sites and the onset of vitellogenin m-RNA synthesis. These observations are in agreement with an earlier report about the increase in the acetylation of histones in fetal guinea pig uterus after oestradiol treatment [1]. The results suggest that the acetylation of histones might be a prerequisite for the removal of structures for efficient gene repression and the establishment of DNase I hypersensitive sites.