PRC2 activates interferon-stimulated genes indirectly by repressing miRNAs in glioblastoma
Autoři:
Haridha Shivram aff001; Steven V. Le aff001; Vishwanath R. Iyer aff001
Působiště autorů:
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Livestrong Cancer Institutes, University of Texas at Austin, Austin, Texas, United States of America
aff001
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222435
Souhrn
Polycomb repressive complex 2 (PRC2) is a chromatin binding complex that represses gene expression by methylating histone H3 at K27 to establish repressed chromatin domains. PRC2 can either regulate genes directly through the methyltransferase activity of its component EZH2 or indirectly by regulating other gene regulators. Gene expression analysis of glioblastoma (GBM) cells lacking EZH2 showed that PRC2 regulates hundreds of interferon-stimulated genes (ISGs). We found that PRC2 directly represses several ISGs and also indirectly activates a distinct set of ISGs. Assessment of EZH2 binding proximal to miRNAs showed that PRC2 directly represses miRNAs encoded in the chromosome 14 imprinted DLK1-DIO3 locus. We found that repression of this locus by PRC2 occurs in immortalized GBM-derived cell lines as well as in primary bulk tumors from GBM and anaplastic astrocytoma patients. Through repression of these miRNAs and several other miRNAs, PRC2 activates a set of ISGs that are targeted by these miRNAs. This PRC2-miRNA-ISG network is likely to be important in regulating gene expression programs in GBM.
Klíčová slova:
Biology and life sciences – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Natural antisense transcripts – MicroRNAs – Messenger RNA – Untranslated regions – 3' UTR – Enzymology – Enzymes – Oxidoreductases – Luciferase – Proteins – Interferons – Genetics – Gene expression – Gene regulation – Genetic loci – Genetic interference
Zdroje
1. Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011;469(7330):343–9. Epub 2011/01/21. doi: 10.1038/nature09784 21248841
2. Cao Q, Mani RS, Ateeq B, Dhanasekaran SM, Asangani IA, Prensner JR, et al. Coordinated regulation of polycomb group complexes through microRNAs in cancer. Cancer Cell. 2011;20(2):187–99. Epub 2011/08/16. doi: 10.1016/j.ccr.2011.06.016 21840484
3. Comet I, Riising EM, Leblanc B, Helin K. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat Rev Cancer. 2016;16(12):803–10. Epub 2016/11/04. doi: 10.1038/nrc.2016.83 27658528
4. Conway E, Healy E, Bracken AP. PRC2 mediated H3K27 methylations in cellular identity and cancer. Curr Opin Cell Biol. 2015;37:42–8. Epub 2015/10/27. doi: 10.1016/j.ceb.2015.10.003 26497635
5. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. Epub 2006/10/25. doi: 10.1038/nrc1997 17060945
6. Polioudakis D, Abell NS, Iyer VR. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes. PLoS One. 2015;10(5):e0126535. Epub 2015/05/21. doi: 10.1371/journal.pone.0126535 25992613
7. Friedman JM, Liang G, Liu CC, Wolff EM, Tsai YC, Ye W, et al. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res. 2009;69(6):2623–9. Epub 2009/03/05. doi: 10.1158/0008-5472.CAN-08-3114 19258506
8. Juan AH, Kumar RM, Marx JG, Young RA, Sartorelli V. Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Mol Cell. 2009;36(1):61–74. Epub 2009/10/13. doi: 10.1016/j.molcel.2009.08.008 19818710
9. Graham B, Marcais A, Dharmalingam G, Carroll T, Kanellopoulou C, Graumann J, et al. MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells. Stem Cell Reports. 2016;6(5):635–42. Epub 2016/05/07. doi: 10.1016/j.stemcr.2016.03.005 27150236
10. Shivram H, Le SV, Iyer VR. MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network. Genome Res. 2019;29(2):184–92. Epub 2019/01/18. doi: 10.1101/gr.238311.118 30651280
11. Das PP, Hendrix DA, Apostolou E, Buchner AH, Canver MC, Beyaz S, et al. PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells. Cell Rep. 2015;12(9):1456–70. Epub 2015/08/25. doi: 10.1016/j.celrep.2015.07.053 26299972
12. Hall AW, Battenhouse AM, Shivram H, Morris AR, Cowperthwaite MC, Shpak M, et al. Bivalent Chromatin Domains in Glioblastoma Reveal a Subtype-Specific Signature of Glioma Stem Cells. Cancer Res. 2018;78(10):2463–74. Epub 2018/03/20. doi: 10.1158/0008-5472.CAN-17-1724 29549165
13. Shivram H, Iyer VR. Identification and removal of sequencing artifacts produced by mispriming during reverse transcription in multiple RNA-seq technologies. RNA. 2018;24(9):1266–74. Epub 2018/06/29. doi: 10.1261/rna.066217.118 29950518
14. Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30(7):923–30. Epub 2013/11/15. doi: 10.1093/bioinformatics/btt656 24227677
15. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. Epub 2014/12/18. doi: 10.1186/s13059-014-0550-8 25516281
16. Abou El Hassan M, Yu T, Song L, Bremner R. Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus. J Immunol. 2015;194(10):5007–13. Epub 2015/04/12. doi: 10.4049/jimmunol.1403247 25862816
17. Boyd NH, Morgan JE, Greer SF. Polycomb recruitment at the Class II transactivator gene. Mol Immunol. 2015;67(2 Pt B):482–91. Epub 2015/08/19. doi: 10.1016/j.molimm.2015.08.003
18. Jin Y, Huo B, Fu X, Hao T, Zhang Y, Guo Y, et al. LSD1 collaborates with EZH2 to regulate expression of interferon-stimulated genes. Biomed Pharmacother. 2017;88:728–37. Epub 2017/02/06. doi: 10.1016/j.biopha.2017.01.055 28152483
19. Aguado LC, Schmid S, Sachs D, Shim JV, Lim JK, tenOever BR. microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection. Cell Host Microbe. 2015;18(6):714–22. Epub 2015/12/15. doi: 10.1016/j.chom.2015.11.003 26651947
20. Holoch D, Margueron R. Mechanisms Regulating PRC2 Recruitment and Enzymatic Activity. Trends Biochem Sci. 2017;42(7):531–42. Epub 2017/05/10. doi: 10.1016/j.tibs.2017.04.003 28483375
21. Natsume A, Ito M, Katsushima K, Ohka F, Hatanaka A, Shinjo K, et al. Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma. Cancer Res. 2013;73(14):4559–70. Epub 2013/05/31. doi: 10.1158/0008-5472.CAN-13-0109 23720055
22. Benetatos L, Hatzimichael E, Londin E, Vartholomatos G, Loher P, Rigoutsos I, et al. The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis. Cell Mol Life Sci. 2013;70(5):795–814. Epub 2012/07/25. doi: 10.1007/s00018-012-1080-8 22825660
23. Abou El Hassan M, Huang K, Eswara MB, Zhao M, Song L, Yu T, et al. Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways. PLoS One. 2015;10(6):e0126466. Epub 2015/06/02. doi: 10.1371/journal.pone.0126466 26030458
24. Escobar TM, Kanellopoulou C, Kugler DG, Kilaru G, Nguyen CK, Nagarajan V, et al. miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression. Immunity. 2014;40(6):865–79. Epub 2014/05/27. doi: 10.1016/j.immuni.2014.03.014 24856900
25. Yanai H, Taniguchi T. Fine-tuning type I IFN signaling: A new chapter in the IFN saga. Cell Res. 2017;27(12):1407–8. Epub 2017/09/20. doi: 10.1038/cr.2017.118 28925385
26. Arbuckle JH, Gardina PJ, Gordon DN, Hickman HD, Yewdell JW, Pierson TC, et al. Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens. MBio. 2017;8(4). Epub 2017/08/16. doi: 10.1128/mBio.01141-17 28811345
Článek vyšel v časopise
PLOS One
2019 Číslo 9
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy