Roles and Regulation of DNA Methylation in Early Mammalian Development.

Abstract

DNA methylation was the earliest epigenetic mark discovered-it is essential for mammalian development and forms a molecular memory that can transcend generations, as in the phenomenon of genomic imprinting. Set against this long-term potential, methylation is dynamic across the life cycle, with genome-wide changes at germ-cell specification, gametogenesis, and preimplantation development accompanying major shifts in cell potency. With a tool kit of precision genetic reagents, the mouse has been a mainstay in developing mechanistic understanding of how methylation is targeted to the genome and in exploring its susceptibility to environmental factors, such as parental diet. The availability of genome sequence from many more species combined with the ability to profile methylation and other epigenetic marks in very small numbers of cells now provides rich epigenomic information from other mammals. This information has begun to reveal both similarities as well as surprising differences in the way in which methylation is patterned across the genome among mammals. Such knowledge will be critical in assessing the outcomes of interventions during assisted reproduction in human clinical practice and livestock production.