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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5369-5381
Number of pages13
JournalOncotarget
Volume6
Issue number7
DOIs
StatePublished - 2015

Keywords

  • Glioblastoma
  • H3K27me3
  • H3K4me3
  • SLC17A7
  • Stem cells

ASJC Scopus subject areas

  • Oncology

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