Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis

Abstract

Dynamic chromatin accessibility regulates stem cell fate determination and tissue homeostasis via controlling gene expression. As a histone-modifying enzyme that predominantly mediates methylation of lysine 27 in histone H3 (H3K27me1/2/3), Polycomb repressive complex 2 (PRC2) plays the canonical role in targeting developmental regulators during stem cell differentiation and transformation. Embryonic ectoderm development (EED), the core scaffold subunit of PRC2 and as an H3K27me3-recognizing protein, has been broadly implicated with PRC2 stabilization and allosterically stimulated PRC2. Accumulating evidences from experimental data indicate that EED-associating epigenetic modifications are indispensable for stem cell maintenance and differentiation into specific cell lineages. In this review, we discuss the most updated advances to summarize the structural architecture of EED and its contributions and underlying mechanisms to mediating lineage differentiation of different stem cells during epigenetic modification to expand our understanding of PRC2.

Research advances of polycomb group proteins in regulating mammalian development

“…The PRC2 core assembling with auxiliary proteins forms two distinct homocomplexes-PRC2.1 and PRC2.2 ( Petracovici and Bonasio, 2021 ; de Potter et al, 2023 ). These auxiliary subunits, including Zinc finger protein AE binding protein 2 (AEBP2), Polycomb-like homologues (PCLs), PRC2-associated LCOR isoform 1 or 2 (PALI1/2), Polycomb repressive complex 2-associated protein (EPOP) and Jumonji and ATrich interaction domain containing 2 (JARID2), contain DNA binding domains which are able to recruit PRC2 to specific genomic loci and allow the adaption of PRC2 to altered cellular states ( Conway et al, 2018 ; Huang et al, 2023 ). PRC2.1 is defined by the presence of one of the three PCLs (PCL1/2 PCL3) and either EPOP or PALI1/2.…”