Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells

Rola Dali, Federica Verginelli, Albena Pramatarova, Robert Sladek, Stefano Stifani

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour-initiating cells (BTICs) with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient-derived BTICs using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH-mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour-promoting functions of FOXG1:TLE1 in GBM.

Original languageEnglish
Pages (from-to)775-787
Number of pages13
JournalMolecular Oncology
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Gene Regulatory Networks
Glioblastoma
Brain Neoplasms
Neoplastic Stem Cells
Survival
Chemotaxis
Neuroglia
Cell Differentiation
Transcription Factors
Maintenance
Cell Proliferation
RNA
Genes
Neoplasms

Keywords

  • CHAC1
  • ChIP-Seq/RNA-Seq
  • FOXG1
  • glioblastoma
  • Groucho/transducin-like Enhancer of split
  • NOTCH

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cancer Research

Cite this

Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells. / Dali, Rola; Verginelli, Federica; Pramatarova, Albena; Sladek, Robert; Stifani, Stefano.

In: Molecular Oncology, Vol. 12, No. 6, 01.06.2018, p. 775-787.

Research output: Contribution to journalArticle

Dali, Rola ; Verginelli, Federica ; Pramatarova, Albena ; Sladek, Robert ; Stifani, Stefano. / Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells. In: Molecular Oncology. 2018 ; Vol. 12, No. 6. pp. 775-787.
@article{5e863a69b5ca4745b383b9bf760cf2e9,
title = "Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells",
abstract = "Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour-initiating cells (BTICs) with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient-derived BTICs using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH-mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour-promoting functions of FOXG1:TLE1 in GBM.",
keywords = "CHAC1, ChIP-Seq/RNA-Seq, FOXG1, glioblastoma, Groucho/transducin-like Enhancer of split, NOTCH",
author = "Rola Dali and Federica Verginelli and Albena Pramatarova and Robert Sladek and Stefano Stifani",
year = "2018",
month = "6",
day = "1",
doi = "10.1002/1878-0261.12168",
language = "English",
volume = "12",
pages = "775--787",
journal = "Molecular Oncology",
issn = "1574-7891",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells

AU - Dali, Rola

AU - Verginelli, Federica

AU - Pramatarova, Albena

AU - Sladek, Robert

AU - Stifani, Stefano

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour-initiating cells (BTICs) with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient-derived BTICs using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH-mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour-promoting functions of FOXG1:TLE1 in GBM.

AB - Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour-initiating cells (BTICs) with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient-derived BTICs using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH-mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour-promoting functions of FOXG1:TLE1 in GBM.

KW - CHAC1

KW - ChIP-Seq/RNA-Seq

KW - FOXG1

KW - glioblastoma

KW - Groucho/transducin-like Enhancer of split

KW - NOTCH

UR - http://www.scopus.com/inward/record.url?scp=85046010394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046010394&partnerID=8YFLogxK

U2 - 10.1002/1878-0261.12168

DO - 10.1002/1878-0261.12168

M3 - Article

VL - 12

SP - 775

EP - 787

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 6

ER -