DNA methylation reprogramming in the germ line

Abstract

In mammals, methylation occurs almost exclusively on the CpG dinucleotide in DNA and shows no preference for sequence context surrounding this target. CpGs are found on many different sequence classes and methylation of this dinucleotide is associated with repression of transcription. Reprogramming methylation in the primordial germ cells establishes monoallelic expression of imprinted genes which exhibit monoallelic expression throughout the lifetime of an organism, maintains retrotransposons in an inactive state and inactivates one of the two X chromosomes. In addition to direct transcriptional silencing, DNA methylation is important for suppression of recombination, and resetting this information is therefore necessary for maintenance of genomic stability. In this chapter, we will review the recent progress in our understanding of the time course and extent of DNA methylation reprogramming of many different sequence classes. We focus on the mouse germline, since this has been the model system from which we have gained the most knowledge of the process. In addition we will examine some of the evidence suggesting a link between repeat methylation and methylation of epigenetically controlled single-copy genes. To do this, we will look at the temporal sequence of methylation events from the time the germ cells become recognizable as a discrete population until the mature male and female gametes fuse and form the early embryo.