Abstract
Dynamic regulation of the chromatin state by Polycomb Repressive Complex 2 (PRC2) provides an important mean for epigenetic gene control that can profoundly influence normal development and cell lineage specification. PRC2 and PRC2-induced methylation of histone H3 lysine 27 (H3K27) are critically involved in a wide range of DNA-templated processes, which at least include transcriptional repression and gene imprinting, organization of three-dimensional chromatin structure, DNA replication and DNA damage response and repair. PRC2-based genome regulation often goes wrong in diseases, notably cancer. This chapter discusses about different modes-of-action through which PRC2 and EZH2, a catalytic subunit of PRC2, mediate (epi)genomic and transcriptomic regulation. We will also discuss about how alteration or mutation of the PRC2 core or axillary component promotes oncogenesis, how post-translational modification regulates functionality of EZH2 and PRC2, and how PRC2 and other epigenetic pathways crosstalk. Lastly, we will briefly touch on advances in targeting EZH2 and PRC2 dependence as cancer therapeutics.
Authors Yiran Guo and Yao Yu have equally contributed to this chapter.
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Acknowledgements
We graciously thank Dr. Shuai Zhao for assistance with illustration of PRC2 structure. This work was supported by National Institutes of Health (NIH) grants awarded to GGW (R01-CA215284 and R01-CA218600). GGW is a Leukemia and Lymphoma Society (LLS) Scholar.
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Guo, Y., Yu, Y., Wang, G.G. (2023). Polycomb Repressive Complex 2 in Oncology. In: Chen, J., Wang, G.G., Lu, J. (eds) Epigenetics in Oncology . Cancer Treatment and Research, vol 190. Springer, Cham. https://doi.org/10.1007/978-3-031-45654-1_9
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