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Polycomb function in early mouse development

Cell Death & Differentiation (2024)Cite this article

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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.

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Fig. 1: Polycomb mechanisms in early mouse development.
Fig. 2: Non-canonical imprinting mechanisms and X chromosome Inactivation (XCI).
Fig. 3: Bivalency establishment and mESC differentiation.
Fig. 4: Schematic representation of the timely activation of the Hox gene clusters during vertebrates somitogenesis.

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Acknowledgements

We thank Pedro Vizán Carralcázar and Pau Pascual-Garcia for critical reading of the manuscript and insightful discussions, and V.A. Raker for scientific editing. We apologize to the authors whose work we could not discuss due to space limitations. We acknowledge funding from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) (PID2022-142679NB-I00 and ‘Planes complementarios’ STOP-DMG N6958), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (FEDER), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713673 “ChromDesign”, “la Caixa” Foundation (HR20-00411), and from AGAUR to L.D.C. The Ramon y Cajal programme of the Ministerio de Ciencia, Innovación y Universidades and the European Social Fund under the reference number RYC-2018-025002-I, the Instituto de Salud Carlos III-FEDER (PI22/01837), and MICIU/AEI /10.13039/501100011033 and NextGeneration EU/PRTR (CNS2023-145726) to S.A. We acknowledge the funding support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya.

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  1. Ivano Mocavini

    Present address: Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA

Authors and Affiliations

  1. Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain

    Livia Condemi, Ivano Mocavini, Sergi Aranda & Luciano Di Croce

  2. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Luciano Di Croce

  3. ICREA, Pg. Lluis Companys 23, 08010, Barcelona, Spain

    Luciano Di Croce

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LC wrote the manuscript and designed figures. IM wrote and revised the manuscript, and designed figures. SA and LDC conceptualized, wrote and revised the manuscript.

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Condemi, L., Mocavini, I., Aranda, S. et al. Polycomb function in early mouse development. Cell Death Differ (2024). https://doi.org/10.1038/s41418-024-01340-3

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