Global analysis of H3K4me3 and H3K27me3 profiles in glioblastoma stem cells and identification of SLC17A7 as a bivalent tumor suppressor gene.
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.
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.|Dept. of Urology, University of Washington, Seattle, WA 98195, USA.|System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang 310058, China.
Biaoyang
B
Lin
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Hwahyung
H
Lee
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Jae-Geun
JG
Yoon
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.|LabCorp Clinical Trials (Genomics Laboratory), Seattle, WA 98109, USA.
Anup
A
Madan
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Elizabeth
E
Wayner
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Sanja
S
Tonning
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Parvinder
P
Hothi
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Brett
B
Schroeder
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Ilya
I
Ulasov
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Gregory
G
Foltz
The Institute for Systems Biology, Seattle, WA 98109, USA.
Leroy
L
Hood
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
Charles
C
Cobbs
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006657:Histones / Q000235:genetics*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D002843:Chromatin; D006657:Histones; D012333:RNA, Messenger; C493464:SLC17A7 protein, human; D050598:Vesicular Glutamate Transport Protein 1
H3K27me3; H3K4me3; SLC17A7; glioblastoma; stem cells