Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development.

Expression and function of homeobox genes (Hox genes) in development have been subject to extensive study in a variety of organisms including mammals, however practically nothing is known regarding the methylation patterns of these genes. Here we describe the methylation patterns of HoxA5 and HoxB5 in various tissues of fetal and adult mice and their relevance to expression. Both genes exhibit tissue specific methylation patterns that are established postnatally. This methylation appears to play a role in stabilizing the newly acquired silent state of the genes. In contrast to the postimplantation wave of de novo methylation that takes place across the mammalian genome, the methylation of the Hox genes represents a different time window for de novo methylation which might be characteristic of developmental genes. In the case of HoxA5 this postnatal de novo methylation can cover a domain of at least 25 kb that includes several genes of the HoxA cluster and the CpG islands within. Our observations suggest that the establishment of tissue specific methylation patterns of HoxA5 and HoxB5 and the relationship between these methylation patterns and activity are different from what had been known for non-developmental genes. This may reflect the specialized functions played by Hox genes in development.