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

// Biaoyang Lin 1, 2, 3 , Hwahyung Lee 4 , Jae-Geun Yoon 4 , Anup Madan 4, 6 , Elizabeth Wayner 4 , Sanja Tonning 4 , Parvinder Hothi 4 , Brett Schroeder 4 , Ilya Ulasov 4 , Gregory Foltz 4 , Leroy Hood 5 , Charles Cobbs 4 1 Cancer 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 2 Dept. of Urology, University of Washington, Seattle, WA 98195, USA 3 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang 310058, China 4 Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA 5 The Institute for Systems Biology, Seattle, WA 98109, USA 6 LabCorp Clinical Trials (Genomics Laboratory), Seattle, WA 98109, USA Correspondence to: 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 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.