Is hypomethylation linked to activation of δ-crystallin genes during lens development?

Expression of many cell type-specific genes is correlated with a reduced level of cytosine methylation^1,2 and some results argue that genetic programmes may be activated by a reduction in DNA methylation³. During embryogenesis, however, when many genes are activated in specific cell lineages, it has not been demonstrated that they are hypomethylated prior to their expression. We have examined the timing of hypomethylation and gene activation during embryonic chick lens development for the two genes encoding δ-crystallin (the major lens-specific protein). We report here that while many of the CCGG sequences analysed become hypomethylated, most do not do so until 2 days after δ-crystallin is first synthesized. However, there is at least one site which is hypomethylated earlier, approximately when transcription is thought to commence. We conclude that hypomethylation in the δ-crystallin genes is probably not a simple process which activates transcription, although early hypomethylation events indicate obvious sites to be examined for a role in gene activation.