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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Biaoyang Lin1,2,3, Hwahyung Lee4, Jae-Geun Yoon4, Anup Madan4,6, Elizabeth Wayner4, Sanja Tonning4, Parvinder Hothi4, Brett Schroeder4, Ilya Ulasov4, Gregory Foltz4, Leroy Hood5, Charles Cobbs4
1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
2Dept. of Urology, University of Washington, Seattle, WA 98195, USA
3System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang 310058, China
4Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA
5The Institute for Systems Biology, Seattle, WA 98109, USA
6LabCorp Clinical Trials (Genomics Laboratory), Seattle, WA 98109, USA
Biaoyang Lin, e-mail: Biaoylin@gmail.com
Keywords: H3K4me3, H3K27me3, glioblastoma, stem cells, SLC17A7
Received: August 22, 2014 Accepted: January 01, 2015 Published: January 22, 2015
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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