Epigenetics in preimplantation mammalian development

Abstract

Fertilization is a very dynamic period of comprehensive chromatin remodeling, from which two specialized cells result in a totipotent zygote. The formation of a totipotent cell requires extensive epigenetic remodeling that, although independent of modifications in the DNA sequence, still entails a profound cell-fate change, supported by transcriptional profile modifications. As a result of finely tuned interactions between numerous mechanisms, the goal of fertilization is to form a full healthy new individual. To avoid the persistence of alterations in epigenetic marks, the epigenetic information contained in each gamete is reset during early embryogenesis. Covalent modification of DNA by methylation, as well as posttranslational modifications of histone proteins and noncoding RNAs, appears to be the main epigenetic mechanisms that control gene expression. These allow different cells in an organism to express different transcription profiles, despite each cell containing the same DNA sequence. In the context of replacement of spermatic protamine with histones from the oocyte, active cell division, and specification of different lineages, active and passive mechanisms of epigenetic remodeling have been revealed as critical for editing the epigenetic profile of the early embryo. Importantly, redundant factors and mechanisms are likely in place, and only a few have been reported as critical for fertilization or embryo survival by the use of knockout models. The aim of this review is to highlight the main mechanisms of epigenetic remodeling that ensue after fertilization in mammals.

Keywords: DNA methylation; Embryo; Histone modifications; Imprinting; Pronucleus; Reprogramming.

Figure 1. DNA methylation dynamics during chromatin replication in the early embryo

A) During cell division in the early embryo two scenarios could happen: i) DNA methylation maintenance (top), where DNMTs recognize the hemimethylated strand and methylate it, ii) absence of DNA methylation maintenance (bottom), so new strand of DNA will be temporarily unmethylated and DNA double helix will result in hemimethylation. In both, de novo DNA methylation and demethylation by hydroximethylation (TET3) or deamination (AID) could take place. B) The activity of TET3 at the maternal PN is limited by the activity of DPPA3 interacting with H3K9me2 which is highly abundant in the maternal PN but not in the paternal PN.

Figure 2

Dynamics of histone modification remodeling in the zygote.