Global analysis of H3K4me3 and H3K27me3 profiles in glioblastoma stem cells and identification of SLC17A7 as a bivalent tumor suppressor gene.
Global analysis of H3K4me3 and H3K27me3 profiles in glioblastoma stem cells and identification of SLC17A7 as a bivalent tumor suppressor gene.
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DOI：
10.18632/oncotarget.3030
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Cobbs C
中科院分区：
文献类型：
--
作者：
Lin B;Lee H;Yoon JG;Madan A;Wayner E;Tonning S;Hothi P;Schroeder B;Ulasov I;Foltz G;Hood L;Cobbs C
表观遗传学改变，包括H3K4me3和H3K27me3组蛋白修饰，在肿瘤发生中起重要作用。然而，尚未为神经胶质瘤生成全基因组的组蛋白修饰图谱。在这里，我们报告了8个胶质瘤干细胞(GSC)系的H3K4me3和H3K27me3组蛋白修饰的全基因组图谱，以及相关基因的激活或抑制模式。此外，我们比较了GSC系和星形胶质细胞的全基因组组蛋白修饰图谱，以确定GSC和星形胶质细胞中独特的基因激活或抑制谱。我们还鉴定了一组二价基因，这些基因与H3K4me3和H3K27me3标记都相关，并准备在胚胎干细胞中发挥作用。作为一种治疗方法，这些二价基因是诱导胶质母细胞瘤分化的潜在靶点。最后，我们确定Slc17a7基因是GBM中的一个二价肿瘤抑制基因，因为它在GBM组织中的蛋白质和RNA水平与正常脑组织相比下调，并抑制GBM细胞的增殖、迁移和侵袭。
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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