Epigenetic genome reprogramming
Epigenetic information is not encoded by the DNA sequence itself but by reversible modifications of DNA and/or histones. Epigenetic mechanisms control the spatial, temporal, and parent-specific gene expression. Different cell types use different patterns of silenced and expressed genes, which are set during development and differentiation and then stably inherited during cell divisions. In general, a cell in the body does not have access to all the information stored in its genome, but only to a small subset (5-10%) of genes. Analogous to computer passwords, epigenetic mechanisms, in particular DNA methylation, regulate the access to this genetic information. In mammals, the paternal and maternal genomes undergo two rounds of parent-specific DNA methylation reprogramming (Fig. 1). Stochastic and/or environmentally induced errors (epimutations) in this highly coordinated process may contribute to human disease. The first round of parent-specific genome reprogramming occurs in the germline. When the primordial germ cells enter the gonadal ridge in the fetus, all DNA methylation patterns are erased, restoring totipotency and an equivalent epigenetic state in germ cells of both sexes. Sex-specific methylation patterns are then established during male versus female germ-cell differentiation. In the second round of genome reprogramming after fertilization the somatic methylation patterns for normal development are created, underlying the activation and silencing of specific genes. Genome-wide demethylation in the zygote and early embryo occurs in a parent-specific manner, broadly affecting different classes of repetitive and single copy sequences. Only imprinted genes are protected by an unknown mechanism against this postzygotic demethylation, maintaining their germline methylation marks and parent-specific activities throughout further development. Imprinted genes are essential for the regulation of fetal and placental growth, somatic differentiation as well as neurological and behavioural functions after birth. Genome-wide de novo methylation occurs preferentially in the inner cell mass of blastocyst embryos, establishing somatic methylation patterns in the precursor cells of the different embryonic lineages.