Abstract
More than 80 years ago, the first Polycomb-related phenotype was identified in Drosophila melanogaster. Later, a group of diverse genes collectively called Polycomb group (PcG) genes were identified based on common mutant phenotypes. PcG proteins, which are well-conserved in animals, were originally characterized as negative regulators of gene transcription during development and subsequently shown to function in various biological processes; their deregulation is associated with diverse phenotypes in development and in disease, especially cancer. PcG proteins function on chromatin and can form two distinct complexes with different enzymatic activities: Polycomb repressive complex 1 (PRC1) is a histone ubiquitin ligase and PRC2 is a histone methyltransferase. Recent studies have revealed the existence of various mutually exclusive PRC1 and PRC2 variants. In this Review, we discuss new concepts concerning the biochemical and molecular functions of these new PcG complex variants, and how their epigenetic activities are involved in mammalian development and cancer.
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Change history
09 May 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41580-022-00495-6
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Acknowledgements
The authors thank the members of the Shilatifard laboratory for insightful discussions and comments. In particular, they thank N. Ethen for the original illustrations, E. Smith for critical review of the manuscript and M. Morgan for editing and scientific suggestions. The work of A.P. is supported by the transition to independence grant K99CA234434. Complex of proteins associated with Set1 (COMPASS)-related and Polycomb group (PcG)-related studies in the Shilatifard laboratory are supported by generous funding from the National Cancer Institute through Outstanding Investigator Award R35CA197569 to A.S.
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A.P. researched data for the article, substantially contributed to discussion of content, wrote the manuscript and edited it before submission. A.S. substantially contributed to discussion of content and reviewed and edited the manuscript before submission.
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Glossary
- Facultative heterochromatin
-
Locus-specific and cell type-specific dense and transcriptionally silenced chromatin.
- Complex variants
-
Multi-protein complexes that share core subunits, but include defining subunits that distinguish one variant from the other.
- Subcomplexes
-
Protein complexes that lack one or more subunits that define the full complex.
- Mutually exclusive
-
Refers to proteins that, even if they interact with a common set of proteins, cannot be found interacting in immunoprecipitation assays followed by western blotting and/or mass spectrometry protein identification.
- Constitutive heterochromatin
-
Very dense and transcriptionally silenced chromatin that is consistently formed (for example, in centromeres) in many cell types.
- CpG islands
-
DNA regions, often corresponding with gene promoters, of several hundred base pairs that contain more than 50% G or C nucleotides and an observed over expected ratio of CpG dinucleotides higher than 0.6.
- Reduced-representation bisulfite sequencing
-
A technique for detecting methylated (or an oxidized form of methylated) cytidine residues. The ‘reduced representation’ allows obtaining information for a limited subset of genomic regions.
- Primitive streak
-
A structure formed in the blastula in the caudal part of the embryo, which is the precursor of the mesoderm.
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Piunti, A., Shilatifard, A. The roles of Polycomb repressive complexes in mammalian development and cancer. Nat Rev Mol Cell Biol 22, 326–345 (2021). https://doi.org/10.1038/s41580-021-00341-1
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DOI: https://doi.org/10.1038/s41580-021-00341-1
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