title: The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation.
abstract: BACKGROUND
  The DEK gene is highly expressed in a wide range of cancer cells, and a recurrent translocation partner in acute myeloid leukemia. While DEK has been identified as one of the most abundant proteins in human chromatin, its function and binding properties are not fully understood.
  
  
  METHODS
  We performed ChIP-seq analysis in the myeloid cell line U937 and coupled it with epigenetic and gene expression analysis to explore the genome-wide binding pattern of DEK and its role in gene regulation.
  
  
  RESULTS
  We show that DEK preferentially binds to open chromatin, with a low degree of DNA methylation and scarce in the heterochromatin marker H3K9me(3) but rich in the euchromatin marks H3K4me(2/3), H3K27ac and H3K9ac. More specifically, DEK binding is predominantly located at the transcription start sites of highly transcribed genes and a comparative analysis with previously established transcription factor binding patterns shows a similarity with that of RNA polymerase II. Further bioinformatic analysis demonstrates that DEK mainly binds to genes that are ubiquitously expressed across tissues. The functional significance of DEK binding was demonstrated by knockdown of DEK by shRNA, resulting in both significant upregulation and downregulation of DEK-bound genes.
  
  
  CONCLUSIONS
  We find that DEK binds to transcription start sites with a dual role in activation and repression of highly and ubiquitously expressed genes.
authors.affiliation: Department of Hematology, Lund University, BMC B13, Klinikgatan 26, 221 84 Lund, Sweden. carl.sanden@med.lu.se.
authors.forename: Carl
authors.initials: C
authors.lastname: Sandén
authors.forename: Linnea
authors.initials: L
authors.lastname: Järvstråt
authors.forename: Andreas
authors.initials: A
authors.lastname: Lennartsson
authors.forename: Per Ludvik
authors.initials: PL
authors.lastname: Brattås
authors.forename: Björn
authors.initials: B
authors.lastname: Nilsson
authors.forename: Urban
authors.initials: U
authors.lastname: Gullberg
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D022423:Myeloid Cells / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D006657:Histones; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012319:RNA Polymerase II