{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":57,"searchCount":0},"additional":{"submitter":["Johnson KM"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["e0186275"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5665490"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(11)"],"pubmed_abstract":["Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI chromosomal translocation. The resulting fusion protein is an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate and repress thousands of target genes mediating oncogenesis. However, the mechanisms of EWS/FLI interaction with microsatellites and regulation of target gene expression is not clearly understood. Here, we profile genome-wide protein binding and gene expression. Using a combination of unbiased genome-wide computational and experimental analysis, we define GGAA-microsatellites in a Ewing sarcoma context. We identify two distinct classes of GGAA-microsatellites and demonstrate that EWS/FLI responsiveness is dependent on microsatellite length. At close range \"promoter-like\" microsatellites, EWS/FLI binding and subsequent target gene activation is highly dependent on number of GGAA-motifs. \"Enhancer-like\" microsatellites demonstrate length-dependent EWS/FLI binding, but minimal correlation for activated and none for repressed targets. Our data suggest EWS/FLI binds to \"promoter-like\" and \"enhancer-like\" microsatellites to mediate activation and repression of target genes through different regulatory mechanisms. Such characterization contributes valuable insight to EWS/FLI transcription factor biology and clarifies the role of GGAA-microsatellites on a global genomic scale. This may provide unique perspective on the role of non-coding DNA in cancer susceptibility and therapeutic development."],"journal":["PloS one"],"pubmed_title":["Identification of two types of GGAA-microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma."],"pmcid":["PMC5665490"],"funding_grant_id":["P30 CA016058","R01 CA140394","R01 CA183776","CA183776","F30 CA210588","CA140394","CA210588"],"pubmed_authors":["Johnson KM","Taslim C","Saund RS","Lessnick SL"],"view_count":["57"],"additional_accession":[]},"is_claimable":false,"name":"Identification of two types of GGAA-microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma.","description":"Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI chromosomal translocation. The resulting fusion protein is an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate and repress thousands of target genes mediating oncogenesis. However, the mechanisms of EWS/FLI interaction with microsatellites and regulation of target gene expression is not clearly understood. Here, we profile genome-wide protein binding and gene expression. Using a combination of unbiased genome-wide computational and experimental analysis, we define GGAA-microsatellites in a Ewing sarcoma context. We identify two distinct classes of GGAA-microsatellites and demonstrate that EWS/FLI responsiveness is dependent on microsatellite length. At close range \"promoter-like\" microsatellites, EWS/FLI binding and subsequent target gene activation is highly dependent on number of GGAA-motifs. \"Enhancer-like\" microsatellites demonstrate length-dependent EWS/FLI binding, but minimal correlation for activated and none for repressed targets. Our data suggest EWS/FLI binds to \"promoter-like\" and \"enhancer-like\" microsatellites to mediate activation and repression of target genes through different regulatory mechanisms. Such characterization contributes valuable insight to EWS/FLI transcription factor biology and clarifies the role of GGAA-microsatellites on a global genomic scale. This may provide unique perspective on the role of non-coding DNA in cancer susceptibility and therapeutic development.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017","modification":"2024-11-19T18:19:22.58Z","creation":"2019-03-27T03:00:34Z"},"accession":"S-EPMC5665490","cross_references":{"pubmed":["29091716"],"doi":["10.1371/journal.pone.0186275"]}}