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Status |
Public on May 13, 2016 |
Title |
Reconstructing gene regulatory networks of tumorigenesis [SNP] |
Organism |
Homo sapiens |
Experiment type |
SNP genotyping by SNP array Genome variation profiling by SNP array
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Summary |
The mechanistic links between transcription factors and the epigenetic landscape, which coordinate the deregulation of gene networks during cell transformation are largely unknown. We used an isogenic model of stepwise tumorigenic transformation of human primary cells to monitor the progressive deregulation of gene networks upon immortalization and oncogene-induced transformation. By combining transcriptome and epigenome data for each step during transformation and by integrating transcription factor (TF) - target gene associations, we identified 142 TFs and 24 chromatin remodelers/modifiers (CRMs), which are preferentially associated with specific co-expression paths that originate from deregulated gene programming during tumorigenesis. These TFs are involved in the regulation of divers processes, including cell differentiation, immune response and establishment/modification of the epigenome. Unexpectedly, the analysis of chromatin state dynamics revealed patterns that distinguish groups of genes, which are not only co-regulated but also functionally related. Further decortication of TF targets enabled us to define potential key regulators of cell transformation, which are engaged in RNA metabolism and chromatin remodelling. Our study suggests a direct implication of CRMs in oncogene-induced tumorigenesis and identifies new CRMs involved in this process. This is the first comprehensive view of gene regulatory networks that are altered during the process of stepwise human cellular tumorigenesis in a virtually isogenic system.
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Overall design |
Affymetrix SNP arrays (250K) were performed according to the manufacturer's directions on DNA extracted from BJ, BJEL and BJELM cells
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Contributor(s) |
Malysheva V, Mendoza-Parra MA, Ashick M, Saleem M, Gronemeyer H |
Citation(s) |
27198694 |
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Submission date |
Aug 31, 2015 |
Last update date |
May 17, 2017 |
Contact name |
Valeriya Malysheva |
E-mail(s) |
Valeriya.MALYSHEVA@igbmc.fr
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Organization name |
IGBMC
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Street address |
1 rue Laurent Fries
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City |
Illkirch; Strasbourg |
ZIP/Postal code |
67404 |
Country |
France |
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Platforms (1) |
GPL3718 |
[Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array |
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Samples (3) |
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This SubSeries is part of SuperSeries: |
GSE72533 |
Reconstructing gene regulatory networks of tumorigenesis |
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Relations |
BioProject |
PRJNA294768 |