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


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Článek vyšel v časopise

PLOS One


2019 Číslo 9
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