title: c-Myb Binding Sites in Haematopoietic Chromatin Landscapes.
abstract: Strict control of tissue-specific gene expression plays a pivotal role during lineage commitment. The transcription factor c-Myb has an essential role in adult haematopoiesis and functions as an oncogene when rearranged in human cancers. Here we have exploited digital genomic footprinting analysis to obtain a global picture of c-Myb occupancy in the genome of six different haematopoietic cell-types. We have biologically validated several c-Myb footprints using c-Myb knockdown data, reporter assays and DamID analysis. We show that our predicted conserved c-Myb footprints are highly dependent on the haematopoietic cell type, but that there is a group of gene targets common to all cell-types analysed. Furthermore, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons. We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes. Our data suggest that c-Myb is a transcription factor with multifaceted target regulation depending on cell type.
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Mads
authors.initials: M
authors.lastname: Bengtsen
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Klepper
authors.affiliation: Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Sveinung
authors.initials: S
authors.lastname: Gundersen
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cuervo
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Finn
authors.initials: F
authors.lastname: Drabløs
authors.affiliation: Department of Informatics, University of Oslo, Oslo, Norway; Department of Tumour Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Geir Kjetil
authors.initials: GK
authors.lastname: Sandve
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Odd Stokke
authors.initials: OS
authors.lastname: Gabrielsen
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Eskeland
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D018983:DNA Footprinting; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006410:Hematopoiesis / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors