DNA methylation: a secondary event in globin gene switching?

Changes in gamma-globin gene methylation accompany the fetal to adult globin switch in man. Using somatic cell hybrids made by fusing mouse erythroleukemia and human fetal erythroid cells, we asked whether methylation is a cause or a consequence of gamma-gene inactivation during development. These hybrids initially express human gamma-globin but switch with time in culture to adult globin gene production. In hybrids before the switch, the gamma-genes are unmethylated. After completion of the switch, the hybrids contain methylated gamma-globin genes. However, during the time that the gamma----beta switch is occurring, hybrids are found that no longer express gamma-globin, yet still possess unmethylated gamma-globin genes. This suggests that methylation is not a primary event in gamma-gene inactivation during human development.