Homeobox genes gain trimethylation of histone H3 lysine 4 in glioblastoma tissue. Issue 3 (17th June 2016)

• Record Type: Journal Article
• Authors: Luo, Kun; Luo, Donghui; Wen, Hao
• Is Part Of: Bioscience reports. Volume 36:Issue 3(2016)
• Publication Date: 2016-06-17
• Subjects: glioblastoma multiforme (GBM) -- H3K4me3 -- homeobox genes; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20160028
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : We revealed that in GBM homeobox genes gain tri-methylation on lysine 4 of histone H3 (H3K4me3), whereas the cell–cell adhesion-related cadherin genes lose H3K4me3, suggesting that the H3K4me3 alteration is related to the formation and migration of GBM cells. Abstract : Glioblastoma multiforme (GBM) exhibits considerable heterogeneity and associates with genome-wide alterations of the repressed chromatin marks DNA methylation and H3 lysine 27 trimethylation (H3K27me3). Tri-methylation on lysine 4 of histone H3 (H3K4me3) is an activating epigenetic mark that is enriched at promoter and promotes expression. It will be helpful in GBM diagnosis and treatment to identify the alteration of H3K4me3 between human GBM and GBM-surrounding tissues. Here, we performed an analysis using next-generation sequencing techniques to identify H3K4me3 modification in a case of GBM and the GBM-surrounding tissues. The results revealed a global decrease in H3K4me3 in GBM, especially at promoters and CpG islands. In GBM, homeobox genes gain H3K4me3, whereas the cell–cell adhesion-related cadherin genes lose H3K4me3. The products of the homeobox genes are highly connected with Ras-signalling and PI3K-Akt signalling pathways. Using The Cancer Genome Atlas (TCGA) data, we inferred the homeobox-regulated genes' expression is higher in 548 GBM cases than in 27 lower grade glioma cases giving that OLIG2 expression can be a reference. The results suggested that the H3K4me3 alteration is related to the formation and migration of GBM cells. We also found an extremely high reads count at epidermal growth factor receptor (EGFR) promoter, probably due to an amplification of copy number. Our analysis provides a case study about the change of H3K4me3 during shift to GBM.