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c-Myb Binding Sites in Haematopoietic Chromatin Landscapes

Bengtsen, Mads; Klepper, Kjetil; Gundersen, Sveinung; Cuervo, Ignacio; Drabløs, Finn; Hovig, Johannes Eivind; Sandve, Geir Kjetil F.; Gabrielsen, Odd Stokke; Eskeland, Ragnhild
Journal article
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URI
http://hdl.handle.net/11250/2372659
Date
2015
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  • Institutt for klinisk og molekylær medisin [3838]
  • Publikasjoner fra CRIStin - NTNU [41935]
Original version
PLoS ONE 2015, 10(7)   10.1371/journal.pone.0133280
Abstract
Strict control of tissue-specific gene expression plays a pivotal role during lineage commit- ment. The transcription factor c-Myb has an essential role in adult haematopoiesis and func- tions 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 foot- prints 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. Further- more, 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 fac- tor with multifaceted target regulation depending on cell type.
Publisher
Public Library of Science
Journal
PLoS ONE

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