Epigenetic regulatory mechanisms during preimplantation development

Abstract

Following fertilization, the newly formed zygote faces several critical decisions regarding cell fate and lineage commitment. First, the parental genomes must be reprogrammed and reset for the zygotic genome to assume responsibility for gene expression. Second, blastomeres must be committed to form either the inner cell mass or trophectoderm before implantation. A variety of epigenetic mechanisms underlies each of these steps, allowing for proper activation of transcriptional circuits which function to specify a cell's identity and maintain or adjust that state as developmental and environmental conditions dictate. These epigenetic mechanisms encompass DNA methylation, post-translational histone modification, chromatin remodeling, and alterations in nuclear architecture. In recent years, stem cells derived from the inner cell mass have been used to examine the epigenetic pathways that regulate pluripotency, differentiation, and lineage commitment. From a technical standpoint, embryonic stem cells provide an easier system to work with compared to preimplantation embryos; however, it is currently unknown how closely the epigenetic mechanisms of cultured stem cells resemble their counterparts in the intact embryo. Furthermore, it remains unclear how similar the reprogramming pathways in artificially created systems, such as nuclear transfer-derived embryos and induced pluripotent stem cells, are to those in naturally created embryos. In this review, we summarize the current knowledge of epigenetic influences during preimplantation development and shed light on the extent to which these pathways are conserved in cultured pluripotent cells in vitro. In doing so, we demonstrate the critical role that epigenetic mechanisms play in the establishment of cell fate during the earliest stages of mammalian development.

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

“…This transition, which is called the maternal-to-zygotic transition, first entails degradation of maternal mRNAs and then activation of the embryonic genome. 40,81,82 Superimposed on genome activation, which results in a dramatic reprogramming of gene expression, is the development of a chromatin-mediated transcriptionally repressive state that is likely critical for generating the correct pattern of gene expression required for continued development. 40 HDACs likely underlie development of the transcriptionally repressive state because inducing histone hyperacetylation using HDAC inhibitors not only relieves the enhancer requirement for efficient expression of plasmid-borne reporter genes in 2-cell embryos, 83,84 but also results in a further increase in global transcription.…”

Supplementation of fetal bovine serum alters histone modification H3R26me2 during preimplantation development of in vitro produced bovine embryos

“…Histone modification is one such epigenetic mechanism that is critical to embryo development of several species such as mice (Corry et al 2009), cattle (Santos et al 2003, Enright et al 2005, Wee et al 2006, Maalouf et al 2008, Ross et al 2008, pig (Park et al 2009, Gao et al 2010, sheep (Hou et al 2008) and human (Zhang et al 2012). In mice, Sarmento et al (2004), describes two types of histone patterns during preimplantation development, a consistent, stable mark during development and a dynamic, reversible mark.…”

Epigenetic mechanisms involved in developmental nutritional programming

“…An association was indeed observed between in vitro conception and changes in DNA methylation, potentially affecting the long-term pattern of expression of genes involved in chronic metabolic disorders, such as obesity and T2D [45] . Thus, identifying the specific features and functions of the epigenetic build-up at these stages and determining the mechanisms by which environmental factors may affect them in the long term will be a major milestone in the domain of DOHaD investigation [69,70] . Post-translational histone modifications have been implicated in the complex changes in gene expression driving early mammalian development.…”