title: Epigenetic features of human mesenchymal stem cells determine their permissiveness for induction of relevant transcriptional changes by SYT-SSX1.
abstract: BACKGROUND
  A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism.
  
  
  RESULTS
  We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression.
  
  
  CONCLUSIONS
  Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects.
authors: Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors: Luisa
authors: L
authors: Cironi
authors: Paolo
authors: P
authors: Provero
authors: Nicola
authors: N
authors: Riggi
authors: Michalina
authors: M
authors: Janiszewska
authors: Domizio
authors: D
authors: Suva
authors: Mario-Luca
authors: ML
authors: Suva
authors: Vincent
authors: V
authors: Kindler
authors: Ivan
authors: I
authors: Stamenkovic
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000502:physiology*; D013584:Sarcoma, Synovial / Q000378:metabolism; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D002843:Chromatin; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D004247:DNA