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  • Review Article
  • Published:

A new world of Polycombs: unexpected partnerships and emerging functions

Nature Reviews Genetics volume 14, pages 853–864 (2013)Cite this article

Subjects

Key Points

  • Many new Polycomb repressive complex 1 (PRC1) components have been identified in mammals and Drosophila melanogaster, which results in alternative complexes that are centred on the E3 ubiquitin-protein ligase RING2; not all of these alternative complexes include a chromodomain-containing Polycomb homologue.

  • Alternative PRC2 complexes have also been discovered in mammals and D. melanogaster.

  • Although much is still unclear, some of these variant complexes may act together. Others have tissue-specific roles in differentiation.

  • Histone H2A ubiquitylation and deubiquitylation are both important for Polycomb group-mediated gene silencing.

  • Mammalian systems reveal multiple strategies of recruitment of PRC1, PRC2 and their variant complexes, including the use of non-coding RNAs, Polycomb response elements and CpG islands.

  • Mutations that affect the methylation of histone H3 lysine 27 (H3K27), as well as mutations in H3K27 itself, reveal surprising effects on both the kinetics of PRC2 function and its role in disease.

  • Enhancer of zeste homologue 2 can methylate non-histone proteins with both activating and repressing effects, which indicates its roles beyond chromatin.

Abstract

Polycomb group (PcG) proteins are epigenetic repressors that are essential for the transcriptional control of cell differentiation and development. PcG-mediated repression is associated with specific post-translational histone modifications and is thought to involve both biochemical and physical modulation of chromatin structure. Recent advances show that PcG complexes comprise a multiplicity of variants and are far more biochemically diverse than previously thought. The importance of these new PcG complexes for normal development and disease, their targeting mechanisms and their shifting roles in the course of differentiation are now the subject of investigation and the focus of this Review.

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Figure 1: Mammalian RING2 complexes.
Figure 2: Alternative enhancer of zeste complexes.
Figure 3: Targeting of Polycomb group complexes.
Figure 4: The roles of Polycomb group proteins in cancer.

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Acknowledgements

The work in the Y.B.S. laboratory is supported by grants from the Swedish Research Council, Carl Tryggers Foundation, Kempestiftelserna, Erik Philip-Sörensens Stiftelse and European Network of Excellence EpiGeneSys. The research of V.P. is supported by the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Molecular Biology, Umeå University, Byggnad 6L, Norrlands University Hospital, 901 87, Umeå, Sweden

    Yuri B. Schwartz

  2. Department of Molecular Biology and Biochemistry, Rutgers University, 604 Allison Road, Piscataway, 08854, New Jersey, USA

    Vincenzo Pirrotta

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Correspondence to Vincenzo Pirrotta.

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Glossary

Homeotic genes

A set of related master transcription regulatory factors that regulate morphogenesis and tissue differentiation.

CpG islands

Vertebrate genomic regions of the order of 1 kb that are rich in CpG dinucleotides; they often lack 5-methylcytosine and frequently correspond to promoter regions.

Embryoid bodies

Three-dimensional aggregates of pluripotent stem cells.

Paralogues

Genes that are originated by a duplication event within the genome.

Orthologues

Genes in different species that are originated from a single gene of the last common ancestor.

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Schwartz, Y., Pirrotta, V. A new world of Polycombs: unexpected partnerships and emerging functions. Nat Rev Genet 14, 853–864 (2013). https://doi.org/10.1038/nrg3603

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