title: Homeobox genes gain trimethylation of histone H3 lysine 4 in glioblastoma tissue.
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.
authors.affiliation: Department of Neurosurgery, Xinjiang Evidence-Based Medicine Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China luokun_2822@sohu.com dr.wenhao@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Luo
authors.affiliation: Department of Neurology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China luokun_2822@sohu.com dr.wenhao@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D005909:Glioblastoma / Q000235:genetics*; D006657:Histones / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000032:analysis / Q000235:genetics*; D008745:Methylation; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D015820:Cadherins; D006657:Histones; D008239:Lysine
keywords: H3K4me3; glioblastoma multiforme (GBM); homeobox genes