Mechanisms of histone H3 lysine 27 trimethylation remodeling during early mammalian development

Abstract

During fertilization, two of the most differentiated cells in the mammalian organism, a sperm and oocyte, are combined to form a pluripotent embryo. Dynamic changes in chromatin structure allow the transition of the chromatin on these specialized cells into an embryonic configuration capable of generating every cell type. Initially, this reprogramming activity is supported by oocyte-derived factors accumulated during oogenesis as proteins and mRNAs; however, the underlying molecular mechanisms that govern it remain poorly characterized. Trimethylation of histone H3 at lysine 27 (H3K27me3) is a repressive epigenetic mark that changes dynamically during pre-implantation development in mice, bovine and pig embryos. Here we present data and hypotheses related to the potential mechanisms behind H3K27me3 remodeling during early development. We postulate that the repressive H3K27me3 mark is globally erased from the parental genomes in order to remove the gametic epigenetic program and to establish a pluripotent embryonic epigenome. We discuss information gathered in mice, pigs, and bovine, with the intent of providing a comparative analysis of the reprogramming of this epigenetic mark during early mammalian development.

Figure 1. Model for H3K27me3 dynamics during early development in late-EGA species. Both active and passive mechanisms are involved in the gradual erasure of H3K27me3. The active mechanism involves maternal JMJD3 mRNA stored in the egg cytoplasm that is rapidly translated after fertilization. The passive mechanism involves the lack of a functional PRC2 before EGA.