Polycomb complexes in stem cells and embryonic development

Abstract

SummaryPolycomb group (PcG) proteins are epigenetic modifiers involved in controlling gene repression. Organized within multiprotein complexes, they regulate developmental genes in multiple cell types and tissue contexts, including embryonic and adult stem cells, and are essential for cell fate transitions and proper development. Here, we summarize recent breakthroughs that have revealed the diversity of PcG complexes acting in different cell types and genomic contexts. Intriguingly, it appears that particular PcG proteins have specific functions in embryonic development, in pluripotent stem cells and in reprogramming somatic cells into a pluripotent-like state. Finally, we highlight recent results from analyzing PcG protein functions in multipotent stem cells, such as neural, hematopoietic and epidermal stem cells. Key words: Polycomb, Stem cells, Transcription, Differentiation, Self-renewal IntroductionAlthough stem cells were discovered decades ago (Till and McCulloch, 1961;Spangrude et al., 1988), their potential as model cells for studying cell differentiation, tissue homeostasis and regeneration has only recently begun to be realized. In particular, embryonic stem cells (ESCs), which are pluripotent cells capable of giving rise to all cell types of the embryo (Boiani and Schöler, 2005), provide a valuable tool for studying embryonic development in vitro.Several transcription factors have been identified as master regulators of pluripotent and multipotent stem cells (Niwa, 2007). Increasing evidence suggests that epigenetic modifications additionally play a crucial role in regulating stem cell characteristics. Among the chromatin modifiers, Polycomb group (PcG) proteins function as gene repressors and are involved in the regulation of stem cell characteristics (Simon and Kingston, 2009). The PcG was originally described as a set of genes responsible for controlling proper body segmentation in Drosophila (Lewis, 1978). During Drosophila embryonic development, PcG proteins repress the homeobox genes of the Hox cluster, thereby determining the proper activation of homeotic genes (Schuettengruber and Cavalli, 2009). The function of PcG proteins as repressors of developmental genes is strongly conserved in mammals (Morey and Helin, 2010). Here, we discuss the latest insights into PcG-mediated epigenetic regulation in stem cells and embryonic development. Molecular activities of PcG complexesIn mammals, PcG proteins are found in several multiprotein complexes (Simon and Kingston, 2009), the best characterized of which are Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) (Margueron and Reinberg, 2011). As epigenetic modifiers, PcG complexes promote gene repression via particular chromatin modifications and compaction (Fig. 1).Here, we provide a brief overview of the molecular mechanisms by which PcG complexes regulate gene expression; for further details, we refer the reader to recent reviews (Lanzuolo and Orlando, 2012;Simon and Kingston, 2013). At the molecular level, PRC2 is responsible for di-and tri-me...

C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

“…Aloia, L., Di Stefano, B., and Di Croce, L. (2013). Polycomb complexes in stem cells and embryonic development.…”

Chromatin regulation: How complex does it get?

“…These epigenetic repressors play a critical role during various developmental processes, such as maintenance of cell identity, stem cell differentiation, and cancer development. 10,11 To exert their repressive function on chromatin, they assemble into multisubunit protein complexes. One of these complexes is polycomb repressive complex (PRC) 1 that was originally described as a single complex in Drosophila.…”

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

“…Poised transcription factories contain Polycomb and RNAPII phosphorylated on Serine5 only, and co-localise with Polycomb-repressed genes 3,4,27 . Polycomb repression plays major roles in pluripotent cells through the silencing of early developmental genes, which are kept in a poised state ready for induction in response to signals that commit cells into specific embryonic lineages 5,28,29 . Polycomb complexes modify histone tails by di-or trimethylation of histone H3K27 residues and monoubiquitinylation of histone H2AK119…”