DEVELOPMENTAL DIFFERENCES IN METHYLATION OF HUMAN ALU REPEATS

Alu repeats are especially rich in CpG dinucleotides, the principal ta rget sites for DNA methylation in eukaryotes. The methylation state of Alus in different human tissues is investigated by simple, direct gen omic blot analysis exploiting recent theoretical and practical advance s concerning Alu sequence evolution. Whereas Alus are almost completel y methylated in somatic tissues such as spleen, they are hypomethylate d in the male germ line and tissues which depend on the differential e xpression of the paternal genome complement for development. In partic ular, we have identified a subset enriched in young Alus whose CpGs ap pear to be almost completely unmethylated in sperm DNA. The existence of this subset potentially explains the conservation of CpG dinucleoti des in active Alu source genes. These profound, sequence-specific deve lopmental changes in the methylation state of Alu repeats suggest a fu nction for Alu sequences at the DNA level, such as a role in genomic i mprinting.