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COMPASS and SWI/SNF complexes in development and disease

Nature Reviews Genetics volume 22, pages 38–58 (2021)Cite this article

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Abstract

The Trithorax group (TrxG) of proteins is a large family of epigenetic regulators that form multiprotein complexes to counteract repressive developmental gene expression programmes established by the Polycomb group of proteins and to promote and maintain an active state of gene expression. Recent studies are providing new insights into how two crucial families of the TrxG — the COMPASS family of histone H3 lysine 4 methyltransferases and the SWI/SNF family of chromatin remodelling complexes — regulate gene expression and developmental programmes, and how misregulation of their activities through genetic abnormalities leads to pathologies such as developmental disorders and malignancies.

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Fig. 1: The evolutionary conservation and composition of the COMPASS histone methyltransferase complexes.
Fig. 2: The evolutionary conservation and complex members of the SWI/SNF chromatin remodellers.
Fig. 3: Subunit switching of BAF complexes during neurogenesis.

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Acknowledgements

The authors thank all members of the Shilatifard laboratory for insightful discussions and comments. In particular, they thank N. Ethen for the illustrations, E. Smith for critical review of the manuscript and M. Morgan for editing and scientific suggestions.

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  1. Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Bercin K. Cenik & Ali Shilatifard

  2. Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Bercin K. Cenik & Ali Shilatifard

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Glossary

Polycomb group (PcG) proteins

Epigenetic regulators that primarily function as transcriptional repressors through two main complexes, Polycomb repressive complex 1 (PRC1) and PRC2.

Paralogs

Two genes are considered paralogs if a gene duplication event leads to their occupation of two different positions in the genome. This is different from a homologue, which is a gene that shares sequence ancestry with another. Homologues can be paralogs or orthologues, which indicates they diverged by speciation.

Polycomb response elements

cis-Regulatory elements that act as a binding platform for both Polycomb group and Trithorax group proteins. Polycomb response elements were first identified in Drosophila melanogaster and are found in several developmentally important genes.

CpG islands

(CGIs). Regions of the genome that have a G/C-rich composition and a high density of the CpG dinucleotide. CGIs span more than 50% of the mammalian genome.

Enhanceropathies

Diseases in which the pathogenesis is driven by misregulation of enhancers.

Genomic instability

The high mutational load of a genome of particular lineage. Changes in DNA sequence, copy number variations and ploidy all contribute to genomic instability. It is typically an underlying or contributing factor to the pathologies of multiple types of diseases, including malignancies and neurodegenerative diseases.

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Cenik, B.K., Shilatifard, A. COMPASS and SWI/SNF complexes in development and disease. Nat Rev Genet 22, 38–58 (2021). https://doi.org/10.1038/s41576-020-0278-0

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