title: The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis.
abstract: BACKGROUND
  SOX2 is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. SOX2 appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of SOX2 in GBM has not yet been defined.
  
  
  RESULTS
  We show that knockdown of the SOX2 gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the SOX2 response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 SOX2 binding regions in the GBM cancer genome. SOX2 binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 SOX2 binding regions. Microarray analysis identified 489 genes whose expression altered in response to SOX2 knockdown. Interesting findings include that SOX2 regulates the expression of SOX family proteins SOX1 and SOX18, and that SOX2 down regulates BEX1 (brain expressed X-linked 1) and BEX2 (brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by SOX2, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and SOX2 form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.
  
  
  CONCLUSIONS
  We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the SOX2 response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of SOX2 in carcinogenesis and serves as a useful resource for the research community.
authors.affiliation: Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Fang
authors.forename: Jae-Geun
authors.initials: JG
authors.lastname: Yoon
authors.forename: Lisha
authors.initials: L
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Jiaofang
authors.initials: J
authors.lastname: Shao
authors.forename: Dasong
authors.initials: D
authors.lastname: Hua
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Gregory
authors.initials: G
authors.lastname: Foltz
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
mesh_terms: D047369:Chromatin Immunoprecipitation; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors