Global analysis of H3K4me3 and H3K27me3 profiles in glioblastoma stem cells and identification of SLC17A7 as a bivalent tumor suppressor gene

胶质母细胞瘤干细胞中 H3K4me3 和 H3K27me3 谱的整体分析以及 SLC17A7 作为双价肿瘤抑制基因的鉴定

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作者:Biaoyang Lin, Hwahyung Lee, Jae-Geun Yoon, Anup Madan, Elizabeth Wayner, Sanja Tonning, Parvinder Hothi, Brett Schroeder, Ilya Ulasov, Gregory Foltz, Leroy Hood, Charles Cobbs

Abstract

Epigenetic changes, including H3K4me3 and H3K27me3 histone modification, play an important role in carcinogenesis. However, no genome-wide histone modification map has been generated for gliomas. Here, we report a genome-wide map of H3K4me3 and H3K27me3 histone modifications for 8 glioma stem cell (GSC) lines, together with the associated gene activation or repression patterns. In addition, we compared the genome-wide histone modification maps of GSC lines to those of astrocytes to identify unique gene activation or repression profiles in GSCs and astrocytes. We also identified a set of bivalent genes, which are genes that are associated with both H3K4me3 and H3K27me3 marks and are poised for action in embryonic stem cells. These bivalent genes are potential targets for inducing differentiation in glioblastoma (GBM) as a therapeutic approach. Finally, we identified SLC17A7 as a bivalent tumor suppressor gene in GBM, as it is down-regulated at both the protein and RNA levels in GBM tissues compared with normal brain tissues, and it inhibits GBM cell proliferation, migration and invasion.

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