Cargando…

The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development

Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive...

Descripción completa

Detalles Bibliográficos
Autores principales: Loh, Chet H., Veenstra, Gert Jan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397020/
https://www.ncbi.nlm.nih.gov/pubmed/35997369
http://dx.doi.org/10.3390/epigenomes6030023
_version_ 1784772043811586048
author Loh, Chet H.
Veenstra, Gert Jan C.
author_facet Loh, Chet H.
Veenstra, Gert Jan C.
author_sort Loh, Chet H.
collection PubMed
description Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development.
format Online
Article
Text
id pubmed-9397020
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93970202022-08-24 The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development Loh, Chet H. Veenstra, Gert Jan C. Epigenomes Review Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development. MDPI 2022-08-12 /pmc/articles/PMC9397020/ /pubmed/35997369 http://dx.doi.org/10.3390/epigenomes6030023 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Loh, Chet H.
Veenstra, Gert Jan C.
The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title_full The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title_fullStr The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title_full_unstemmed The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title_short The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
title_sort role of polycomb proteins in cell lineage commitment and embryonic development
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397020/
https://www.ncbi.nlm.nih.gov/pubmed/35997369
http://dx.doi.org/10.3390/epigenomes6030023
work_keys_str_mv AT lohcheth theroleofpolycombproteinsincelllineagecommitmentandembryonicdevelopment
AT veenstragertjanc theroleofpolycombproteinsincelllineagecommitmentandembryonicdevelopment
AT lohcheth roleofpolycombproteinsincelllineagecommitmentandembryonicdevelopment
AT veenstragertjanc roleofpolycombproteinsincelllineagecommitmentandembryonicdevelopment