Epigenetics in preimplantation mammalian development

Abstract

Fertilization is a very dynamic period of comprehensive chromatin remodelling, from which two specialized cells result in a totipotent zygote. The formation of a totipotent cell requires extensive epigenetic remodeling that, while 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 post-translational modifications of histone proteins and non-coding RNAs, appear 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.

Functional Human Oocytes Generated by Transfer of Polar Body Genomes

“…This process undergoes dynamic changes during and after fertilization reflecting developmental reprogramming (Canovas and Ross, 2016). Also, the establishment of stable ESCs is associated with major changes in methylation profiles as the genome reconfigures to the pluripotent state (Lister et al, 2009;Lister et al, 2011;Ma et al, 2014).…”

A Resource for the Allele-Specific Analysis of DNA Methylation at Multiple Genomically Imprinted Loci in Mice

“…Recently, a number of proteins have been demonstrated to directly regulate multiple imprinted loci. These include, but are not limited to, Dnmt3l, Dnmt1, Lsd2, Trim28, Zfp57 , and Tet1/2 , each with a different mechanism of action (Bourc’his et al 2001; Howell et al 2001; Reik et al 2003; Li et al 2008a; Karytinos et al 2009; Fang et al 2010; Messerschmidt et al 2012; Yamaguchi et al 2013; Canovas and Ross 2016). For example, deletion of the regulatory subunit of the de novo DNA methyltransferase Dnmt3L results in the failure to establish maternal DNA methylation at a number of maternally imprinted loci, including Peg3, Lit1/Kcnq1ot1 and Snrpn (Bourc’his et al 2001; Hata et al 2002).…”

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

“…The erasure of DNA methylation during reprogramming is extensive (particularly in PGCs), but some DNA methylation persists and paves the way for possible epigenetic inheritance. While differential methylated regions (DMRs) for imprinted genes with a gender-dependent predefinition to possess DNA methylation in offspring can be protected from the DNA demethylation process that occurs immediately after fertilization, escapees represent genomic regions protected from reprogramming-associated demethylation during both the PGC and preimplantation stages (Marcho et al 2015, Canovas & Ross 2016, Tang et al 2016, Voon & Gibbons 2016. Most escapees are associated with retrotransposable elements (e.g., intracisternal A particle (IAP) elements in mice and SINE7-VNTR-ALU (SVA) elements in humans (Lane et al 2003, Tang et al 2015).…”