1. Rasoul Godini, Hossein Fallahi
Epigenome And Transcriptome Analysis Revealed Core Regulatory Network Involved In Glioblastoma
Rasoul Godini, Hossein Fallahi
Dep. of Biology, School of Sciences, Razi University, Baq-e-Abrisham, Kermanshah, Iran.
Objectives
Glioblastoma is a main type of brain tumors that derived from astrocytes. Glioblastoma are classified as very aggressive cancers with no clear cause. Transcriptome of the cancerous cells dramatically differs from normal ones. On the other hand, role of epigenetic alterations has been shown in cancer development. Here, using bioinformatics and biostatistics, we have analyzed transcriptome and epigenome data of 4 glioblastoma specimens to reveal main transcription factors (TFs) and their epigenetic status. Additionally, we have constructed a core regulatory network for glioblastoma.
Figure 5. Gene ontology of core TF targets.
Methylation level
Figure 2. Hierarchical clustering of all TFs in all considered samples based similarity
Methods
To do this study, we used dataset GSE46016 which covers several samples for transcriptome, methylome, and histone modification data for 4 brain tumor samples, neural stem cells and normal astrocytes samples. Using GEO2R tool of NCBI compared tumor samples against astrocytes and applying FDR equal or less than 0.01 and log2FC 0.6 and 1.5 DE genes were detected. We used hierarchical clustering to cluster the TFs and predict differentially expressed TFs (DE-TFs), which are controlling all other TFs using Enrichr database. Core regulatory network of main TFs were constructed and analyzed with Cytoscape program to find hub TFs. Afterward, methylation status and histone modifications were considered to confirm transcriptome findings.
Figure 6. Methylation level and corresponding log2 fold change of expression of the core TFs.
Results
Our analysis revealed that there are 119 common TFs in all tumor samples. Using data of ChEA and ENCODE databases, we predicted 22 DE-TFs controlling all other TFs. Despite of almost revers pattern of gene expression in one of the samples, we found 7 TFs, including ZNF217, TCF4, and JUN, up-regulated in glioblastoma. Almost all target genes of these TFs were up-regulated, as well. Gene ontology revealed that this genes are related to apoptosis and neuron differentiation and migration. Methylome analysis of upstream these TFs showed hypomethylation of DMRs. H3K27me3 and H3K4me3 modifications were majors for most of the TFs.
Figure 3. Core regulatory network that controls all other TFs in glioblastoma, either up- or down regulated.
References
Conclusions
In conclusion, using transcriptome and epigenome data, we have detected several hub TFs significantly involved in glioblastoma, which confirm previous findings and also predict potentially important candidates for further studies.
Figure 4. Histone modification of up- and down regulated TFs in glioblastoma samples.
Figure 1. Veen diagram of common TFs among
glioblastoma samples
Poster No. 756