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A Structural Perspective on Gene Repression by Polycomb Repressive Complex 2

Overview
Journal Subcell Biochem
Publisher Springer
Specialty Biochemistry
Date 2020 Nov 30
PMID 33252743
Citations 5
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Abstract

Polycomb Repressive Complex 2 (PRC2) is a major repressive chromatin complex formed by the Polycomb Group (PcG) proteins. PRC2 mediates trimethylation of histone H3 lysine 27 (H3K27me3), a hallmark of gene silencing. PRC2 is a key regulator of development, impacting many fundamental biological processes, like stem cell differentiation in mammals and vernalization in plants. Misregulation of PRC2 function is linked to a variety of human cancers and developmental disorders. In correlation with its diverse roles in development, PRC2 displays a high degree of compositional complexity and plasticity. Structural biology research over the past decade has shed light on the molecular mechanisms of the assembly, catalysis, allosteric activation, autoinhibition, chemical inhibition, dimerization and chromatin targeting of various developmentally regulated PRC2 complexes. In addition to these aspects, structure-function analysis is also discussed in connection with disease data in this chapter.

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References
1.
AlHaj Abed J, Jones R . H3K36me3 key to Polycomb-mediated gene silencing in lineage specification. Nat Struct Mol Biol. 2012; 19(12):1214-5. PMC: 4019213. DOI: 10.1038/nsmb.2458. View

2.
Abel K, Brody L, Valdes J, Erdos M, McKinley D, Castilla L . Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1. Genomics. 1996; 37(2):161-71. DOI: 10.1006/geno.1996.0537. View

3.
Alekseyenko A, Gorchakov A, Kharchenko P, Kuroda M . Reciprocal interactions of human C10orf12 and C17orf96 with PRC2 revealed by BioTAP-XL cross-linking and affinity purification. Proc Natl Acad Sci U S A. 2014; 111(7):2488-93. PMC: 3932854. DOI: 10.1073/pnas.1400648111. View

4.
Al-Salem A, Alshammari M, Hassan H, AlAzami A, Alkuraya F . Weaver syndrome and defective cortical development: a rare association. Am J Med Genet A. 2012; 161A(1):225-7. DOI: 10.1002/ajmg.a.35660. View

5.
Aloia L, Di Stefano B, Di Croce L . Polycomb complexes in stem cells and embryonic development. Development. 2013; 140(12):2525-34. DOI: 10.1242/dev.091553. View