title: EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions.
abstract: BACKGROUND
  FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.
  
  
  RESULTS
  To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level.
  
  
  CONCLUSIONS
  The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes involved in pathways at the RNA regulatory level with potential to mediate normal and disease-associated functions of the FUS and EWS proteins.
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. alun@biomed.au.dk.
authors.forename: Yonglun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. Jenny.Friis@rsyd.dk.|Present address: Clinical Microbiological Section, Lillebælt Hospital, Vejle, Denmark. Jenny.Friis@rsyd.dk.
authors.forename: Jenny
authors.initials: J
authors.lastname: Blechingberg
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. anamiguel.fernandes@mdc-berlin.de.|Present address: Epigenetic Regulation and Chromatin Architecture group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany. anamiguel.fernandes@mdc-berlin.de.
authors.forename: Ana Miguel
authors.initials: AM
authors.lastname: Fernandes
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. shengting@biomed.au.dk.|Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. shengting@biomed.au.dk.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark. shengting@biomed.au.dk.
authors.forename: Shengting
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. tue@biomed.au.dk.|Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. tue@biomed.au.dk.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark. tue@biomed.au.dk.
authors.forename: Tue
authors.initials: T
authors.lastname: Fryland
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. anders@biomed.au.dk.|Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.|Psychiatric Department P, Aarhus University Hospital, Aarhus, Denmark. anders@biomed.au.dk.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. bolund@biomed.au.dk.|Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. bolund@biomed.au.dk.|BGI-Shenzhen, Shenzhen, China. bolund@biomed.au.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.affiliation: Department of Biomedicine, Aarhus University, The Bartholin Building, Aarhus, DK-8000, Denmark. aln@biomed.au.dk.|Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. aln@biomed.au.dk.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark. aln@biomed.au.dk.
authors.forename: Anders Lade
authors.initials: AL
authors.lastname: Nielsen
mesh_terms: D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D012313:RNA / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C000599550:FUS protein, human; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D012313:RNA