DNA Methylation and the Inactive X Chromosome of Mammals

Abstract

In 1949 Barr and Bertram (1949) reported that the neurons of female cats contained a peculiar body of heterochromatin adjacent to the nuclear membrane which was absent in cells of the males. Later studies showed that many somatic cells of female mammals had this body. In 1960 Taylor using ³H-thymidine and autoradiography reported that the two X chromosomes of Chinese hamster females were different in the pattern of DNA replication. The long arm of one X, which is heterochromatic, is replicated late in S phase while the short euchromatic arm and the whole of the other X chromosome is replicated in the first half of the S phase. The single X in a culture of male somatic cells is replicated in the first half of S phase, similar to the early replicating X in female cells. At about the same time Lyon (1961), who had been studying the coat color variegation by a gene translocated from an autosome to the X chromosome in mice, explained her results on the hypothesis that one X chromosome is inactivated and that the heterochromatic Barr body represented that chromosome. She was unaware at that time of the difference in patterns of replication, but German (1962) who knew about the work on replication reported that one human X chromosome was late replicating and suggested the connection to the Barr body. Additional autoradiographic studies of replication patterns and karyotypes from humans with aberrant X or Y chromosomes showed that all but one X is late replicating in either females or males with two or more X chromosomes.