Polycomb group proteins in cancer: multifaceted functions and strategies for modulation

Wang, Sijie; Ordonez-Rubiano, Sandra C.; Dhiman, Alisha; Jiao, Guanming; Strohmier, Brayden P.; Krusemark, Casey J.; Dykhuizen, Emily C.

doi:10.1093/narcan/zcab039

Cited by 12 publications

(12 citation statements)

References 303 publications

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“…RNF2 and EZH2 belong to the Polycomb-group (PcG) family, which has been demonstrated to regulate the expression and function of several oncogenes and tumour suppressor genes and has been linked to cancer patient survival [32]. Targeting the polycomb machinery, through pharmacological or genetic means, has been proposed as a promising approach for cancer therapy [32, 33].…”

Section: Resultsmentioning

confidence: 99%

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

Nkhoma,

Dzobo,

Kafita

et al. 2023

Preprint

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Acute myeloid leukaemia (AML) is a heterogeneous disease with complex pathogenesis that affects hematopoietic stem cells. Ethnic and racial disparities have been reported to affect treatment and survival outcomes in AML patients. Here, we analysed clinical and transcriptomic data from The Cancer Genome Atlas (TCGA) to investigate potential differences in the genetic landscape of AML between African and European individuals. We found several differentially expressed mRNA transcripts between the AML of Africans and Europeans. Notably, AML in African patients exhibited enrichment for several pathways, including signalling by G-protein-coupled receptors, oncostatin M, and codeine and morphine metabolism. In contrast, AML in European patients showed enrichment for pathways related to the glial cell-line derived neurotrophic factor/rearranged during transfection signalling axis, gamma-aminobutyric acid receptor activation, and ligand-gated ion transport channels. Additionally, kinase enrichment analysis identified shared and distinct kinases in AML among Africans and Europeans: Africans showed an enrichment of cyclin-dependent kinases, while Europeans exhibited an enrichment of ULK2, CSNK2B, and CAMK1. Our study highlights the potential importance of considering race when evaluating the genetic landscape of AML, which may improve treatment strategies for this disease.

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Section: Resultsmentioning

confidence: 99%

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

Nkhoma,

Dzobo,

Kafita

et al. 2023

Preprint

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“…significant loss H3K36me3 and H3K27me3 methylation upon infection. Polycomb repressive complex 2 (PRC2) is responsible for H3K27 methylation via the EZH2 methyltransferase [ 72 ] which is deregulated in multiple cancers [ 73 ]. H3K36me3 marks the body of actively transcribing genes and plays a role transcriptional fidelity, mRNA splicing and DNA damage repair and is mutated in some human tumours [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Putative SET-domain methyltransferases inCryptosporidium parvumand histone methylation during infection

et al. 2022

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Cryptosporidium parvum is a leading cause of diarrhoeal illness worldwide being a significant threat to young children and immunocompromised patients, but the pathogenesis caused by this parasite remains poorly understood. C. parvum was recently linked with oncogenesis. Notably, the mechanisms of gene expression regulation are unexplored in Cryptosporidium and little is known about how the parasite impact host genome regulation. Here, we investigated potential histone lysine methylation, a dynamic epigenetic modification, during the life cycle of the parasite. We identified SET-domain containing proteins, putative lysine methyltransferases (KMTs), in the C. parvum genome and classified them phylogenetically into distinct subfamilies (namely CpSET1, CpSET2, CpSET8, CpKMTox and CpAKMT). Our structural analysis further characterized CpSET1, CpSET2 and CpSET8 as histone lysine methyltransferases (HKMTs). The expression of the CpSET genes varies considerably during the parasite life cycle and specific methyl-lysine antibodies showed dynamic changes in parasite histone methylation during development (CpSET1:H3K4; CpSET2:H3K36; CpSET8:H4K20). We investigated the impact of C. parvum infection on the host histone lysine methylation. Remarkably, parasite infection led to a considerable decrease in host H3K36me3 and H3K27me3 levels, highlighting the potential of the parasite to exploit the host epigenetic regulation to its advantage. This is the first study to describe epigenetic mechanisms occurring throughout the parasite life cycle and during the host–parasite interaction. A better understanding of histone methylation in both parasite and host genomes may highlight novel infection control strategies.

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“…As histone modifications introduced by PRCs are heritable during mitotic cell divisions (reviewed in the work of [ 16 , 17 , 18 ]), PRCs provide an epigenetic memory system required for stable cell identity, for an adequate response to external cues, and even for stable repression of genomic repeats (reviewed in the work of [ 19 ]). In line with its function in cell identity maintenance in animals, PRC2 dysfunction is frequently associated with cancer development and PRC2 is a potent target for anticancer therapy (reviewed in the work of [ 20 , 21 , 22 ]).…”

Section: Introductionmentioning

confidence: 99%

Polycomb Repressive Complex 2 in Eukaryotes—An Evolutionary Perspective

2022

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Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals and plants. The composition, biochemistry, and developmental function of PRC2 in animal and flowering plant model species are relatively well described. Recent evidence demonstrates the presence of PRC2 complexes in various eukaryotic supergroups, suggesting conservation of the complex and its function. Here, we provide an overview of the current understanding of PRC2-mediated repression in different representatives of eukaryotic supergroups with a focus on the green lineage. By comparison of PRC2 in different eukaryotes, we highlight the possible common and diverged features suggesting evolutionary implications and outline emerging questions and directions for future research of polycomb repression and its evolution.

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Polycomb group proteins in cancer: multifaceted functions and strategies for modulation

Cited by 12 publications

References 303 publications

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

Putative SET-domain methyltransferases inCryptosporidium parvumand histone methylation during infection

Polycomb Repressive Complex 2 in Eukaryotes—An Evolutionary Perspective

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