Polycomb function in early mouse development

Abstract

Epigenetic factors are crucial for ensuring proper chromatin dynamics during the initial stages of embryo development. Among these factors, the Polycomb group (PcG) of proteins plays a key role in establishing correct transcriptional programmes during mouse embryogenesis. PcG proteins are classified into two complexes: Polycomb repressive complex 1 (PRC1) and PRC2. Both complexes decorate histone proteins with distinct post-translational modifications (PTMs) that are predictive of a silent transcriptional chromatin state. In recent years, a critical adaptation of the classical techniques to analyse chromatin profiles and to study biochemical interactions at low-input resolution has allowed us to deeply explore PcG molecular mechanisms in the very early stages of mouse embryo development- from fertilisation to gastrulation, and from zygotic genome activation (ZGA) to specific lineages differentiation. These advancements provide a foundation for a deeper understanding of the fundamental role Polycomb complexes play in early development and have elucidated the mechanistic dynamics of PRC1 and PRC2. In this review, we discuss the functions and molecular mechanisms of both PRC1 and PRC2 during early mouse embryo development, integrating new studies with existing knowledge. Furthermore, we highlight the molecular functionality of Polycomb complexes from ZGA through gastrulation, with a particular focus on non-canonical imprinted and bivalent genes, and Hox cluster regulation.

Fig. 1. Polycomb mechanisms in early mouse development.

A Representation of mouse embryo development from E0.5 to E5.5, with main embryo cell names shown. B Genomic distribution of H3K4me3, H2Aub and H3K27me3 during embryo development, focusing on two different sets of genes: developmental genes and gene desert sequences. C Mechanisms of PcG protein recruitment during early developmental stages.

Fig. 2. Non-canonical imprinting mechanisms and X chromosome Inactivation (XCI).

A Establishment of non-canonical imprinted genes on maternal imprinting control regions (ICRs) from the fully grown oocytes until their discharge at E6.5, with the recruitment mechanism of PRC1 and PRC2. B Xist as an example of maternal imprinted gene, which regulates paternal XCI in the female morula (E3). PRC1 and PRC2 are recruited onto the paternal X chromosome through Xist and are involved in mediating the X inactivation.

Fig. 3. Bivalency establishment and mESC differentiation.

A PRC2 recruitment to bivalent promoters, following their mechanisms through embryo development and mESC differentiation. B Representation of mESCs and in vitro differentiated cells.

Fig. 4. Schematic representation of the timely activation of the Hox gene clusters during vertebrates somitogenesis.

A, B Two hypothetical mechanisms to explain the Polycomb phenotype are presented.