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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.
This article was published in the following journal.
Name: PloS one
MicroRNAs (miRNAs) are naturally occurring, highly conserved families of transcripts (∼22 nucleotides in length) that are processed from larger hairpin precursors. miRNAs primarily regulate gene exp...
The phenotypes caused by morpholino-mediated interference of gene function in zebrafish are often not observed in the corresponding mutant(s). We took advantage of the availability of a relatively lar...
Interferons (IFNs) play crucial roles in the development and treatment of cancer. Long non-coding RNAs (lncRNAs) are emerging molecules involved in cancer progression. Here, we identified and characte...
MicroRNAs (miRNAs) modulate the abundance and spatial-temporal accumulation of target mRNAs and indirectly regulate several plant processes. Transcriptional regulation of the genes encoding miRNAs (MI...
G3BPs are members of an RNA-binding protein family and their aberrant expression is common in various cancers and there is growing evidence that G3BPs possess antiviral activities and are targeted by ...
The chief purpose of this research is to evaluate interferon alpha sensitivity and cell type specific levels of interferon receptor and interferon stimulated genes and proteins in HIV/ HCV...
The study is to optimize the clinical therapeutic pathway of peginterferon alfa-2a treatment in patients with chronic hepatitis B based on the detection of interferon gene mutation (IFNA2p...
The objectives are to: 1. derive and validate a panel of miRNAs that are consistently differentially expressed in the plasma of patients with and without sepsis 2. investi...
To find out which of four doses of (recombinant) human interferon gamma (IFN-G) is most effective in stimulating the white blood cells (monocytes) to fight infection and to see if treatmen...
The purpose of this study is to identify predictors and associated biochemical markers of interferon-induced depression. It is hypothesized that genetic variation in genes related to the ...
An interferon regulatory factor that is induced by INTERFERONS as well as LMP-1 protein from EPSTEIN-BARR VIRUS. IRF-7 undergoes PHOSPHORYLATION prior to nuclear translocation and it activates GENETIC TRANSCRIPTION of multiple interferon GENES.
An interferon regulatory factor that recruits STAT1 PROTEIN and STAT2 PROTEIN heterodimers to interferon-stimulated response elements and functions as an immediate-early protein.
A multimeric complex that functions as a ligand-dependent transcription factor. ISGF3 is assembled in the CYTOPLASM and translocated to the CELL NUCLEUS in response to INTERFERON signaling. It consists of ISGF3-GAMMA and ISGF3-ALPHA, and it regulates expression of many interferon-responsive GENES.
An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes.
A family of transcription factors that share an N-terminal HELIX-TURN-HELIX MOTIF and bind INTERFERON-inducible promoters to control GENE expression. IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence.
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...