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Title: Genome-wide chromatin binding of MYC, Omomyc, RNA polymerase II (Pol II), and Pol II Ser-2p in human glioblastoma cells and glioblastoma stem cells expressing or not Omomyc      
keywords:
Epigenomics
ID:
PRJNA342118
description:
MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programs but its activity is not clearly understood. We address MYC function in cancer stem cells through the inducible expression of Omomyc – a MYC derived polypeptide interfering with MYC activity – taking as model the most lethal brain tumor, glioblastoma. Omomyc bridles the key cancer stem-like cell features and affects tumor microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper Myc localization and binds to DNA, with a preference for sites previously occupied by MYC. This is accompanied by (leads to) selective repression of master transcription factors for glioblastoma stem-like cell identity like POU3F2, SOX2, and OLIG2, upregulation of effectors of tumor suppression and differentiation such as PTEN, ID4, MIAT, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion like EGFR and ZEB1. Data support a novel view of MYC as a network stabilizer that strengthens the regulatory nodes of the gene expression programs controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells. Overall design: We employed patient-derived glioblastoma stem cells BT168 and the human glioblastoma cell line U-87 MG, each harboring a Doxycycline-inducible FLAG-Omomyc construct (FO), to study through ChIP-seq the chromatin binding sites of MYC, Omomyc, RNA Pol II, and RNA Pol II phospho Ser-2, in the presence or absence of Omomyc. ChIP enriched and input genomic DNAs were sequenced by Illumina HiSeq 2000 platform. The study includes 21 samples.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA342118
authentication:
none
authorization:
none
ID:
pmid:27852622
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject