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Polycomb Repressive Complex 2: a Dimmer Switch of Gene Regulation in Calvarial Bone Development

  • Skeletal Development (R Marcucio and J Feng, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Epigenetic regulation is a distinct mechanism of gene regulation that functions by modulating chromatin structure and accessibility. Polycomb Repressive Complex 2 (PRC2) is a conserved chromatin regulator that is required in the developing embryo to control the expression of key developmental genes. An emerging feature of PRC2 is that it not only allows for binary ON/OFF states of gene expression but can also modulate gene expression in feed-forward loops to change the outcome of gene regulatory networks. This striking feature of epigenetic modulation has improved our understanding of musculoskeletal development.

Recent Findings

Recent advances in mouse embryos unravel a range of phenotypes that demonstrate the tissue-specific, temporal, and spatial role of PRC2 during organogenesis and cell fate decisions in vivo. Here, we take a detailed view of how PRC2 functions during the development of calvarial bone and skin.

Summary

Based on the emerging evidence, we propose that PRC2 serves as a “dimmer switch” to modulate gene expression of target genes by altering the expression of activators and inhibitors. This review highlights the findings from contemporary research that allow us to investigate the unique developmental potential of intramembranous calvarial bones.

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Funding

Funding is provided by NIH-NIDCR R01-DE18470 (RA), NIH-NIAMS T32 fellowship AR-007505 (JF).

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Authors and Affiliations

  1. Department of Biology, Case Western Reserve University, Cleveland, OH, USA

    Timothy Nehila, James W. Ferguson & Radhika P. Atit

  2. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA

    Radhika P. Atit

  3. Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA

    Radhika P. Atit

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  1. Timothy Nehila
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  2. James W. Ferguson
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Correspondence to Radhika P. Atit.

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Timothy Nehila, James W. Ferguson, and Radhika P. Atit declare no conflict of interest.

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Significance

In order to efficiently and effectively apply orthopedic stem cell therapies, an in-depth understanding of specific genetic regulatory networks (GRN) in distinct musculoskeletal cell populations is essential. Epigenetic regulation is a “tool” that can be used to modulate regulation of GRN in order to alter cell differentiation programs. Manipulating epigenetic mechanisms has the potential to reveal new functions of GRN components that were not discernible by traditional loss- and gain-of-function approaches. Thus, the new knowledge gained from investigating epigenetic regulation of developing calvarial bone program and other tissues’ programs will inform tissue engineering and improve outcomes of genetic therapies in orthopedics.

This article is part of the Topical Collection on Skeletal Development

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Nehila, T., Ferguson, J.W. & Atit, R.P. Polycomb Repressive Complex 2: a Dimmer Switch of Gene Regulation in Calvarial Bone Development. Curr Osteoporos Rep 18, 378–387 (2020). https://doi.org/10.1007/s11914-020-00603-5

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