Mammalian epigenomics: reprogramming the genome for development and therapy

Abstract

Epigenetic modifications of DNA and chromatin are important for genome function during development and in adults. DNA and chromatin modifications have central importance for genomic imprinting and other aspects of epigenetic control of gene expression. In somatic lineages, modifications are generally stably maintained and are characteristic of different specialized tissues. The mammalian genome undergoes major reprogramming of modification patterns in germ cells and in the early embryo. Some of the factors that are involved both in maintenance and in reprogramming, such as methyltransferases, are being identified. Epigenetic reprogramming is deficient in animal cloning, which is a major explanation for the inefficiency of the cloning procedure. Deficiencies in reprogramming are likely to underlie the occurrence of epimutations and of epigenetic inheritance. Environmental factors can alter epigenetic modifications and may thus have long-lasting effects on phenotype. Epigenomics methods are being developed to catalogue genome modifications under normal and pathological conditions. Epigenetic engineering is likely to play an important role in medicine in the future.