Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB.

Autor: Lemma RB; Department of Biosciences, University of Oslo, Blindern, PO Box 1066, 0316, Oslo, Norway.; Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, 0318, Oslo, Norway., Ledsaak M; Department of Biosciences, University of Oslo, Blindern, PO Box 1066, 0316, Oslo, Norway.; Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Blindern, PO Box 1112, 0317, Oslo, Norway., Fuglerud BM; Department of Biosciences, University of Oslo, Blindern, PO Box 1066, 0316, Oslo, Norway.; Terry Fox Laboratory, BC Cancer, Vancouver, BC, V5Z 1L3, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada., Sandve GK; Department of Informatics, University of Oslo, Blindern, PO Box 1080, 0371, Oslo, Norway., Eskeland R; Department of Biosciences, University of Oslo, Blindern, PO Box 1066, 0316, Oslo, Norway.; Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Blindern, PO Box 1112, 0317, Oslo, Norway.; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Gabrielsen OS; Department of Biosciences, University of Oslo, Blindern, PO Box 1066, 0316, Oslo, Norway. o.s.gabrielsen@ibv.uio.no.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Apr 26; Vol. 11 (1), pp. 9008. Date of Electronic Publication: 2021 Apr 26.
DOI: 10.1038/s41598-021-88516-w
Abstrakt: The transcription factor MYB is a master regulator in haematopoietic progenitor cells and a pioneer factor affecting differentiation and proliferation of these cells. Leukaemic transformation may be promoted by high MYB levels. Despite much accumulated molecular knowledge of MYB, we still lack a comprehensive understanding of its target genes and its chromatin action. In the present work, we performed a ChIP-seq analysis of MYB in K562 cells accompanied by detailed bioinformatics analyses. We found that MYB occupies both promoters and enhancers. Five clusters (C1-C5) were found when we classified MYB peaks according to epigenetic profiles. C1 was enriched for promoters and C2 dominated by enhancers. C2-linked genes were connected to hematopoietic specific functions and had GATA factor motifs as second in frequency. C1 had in addition to MYB-motifs a significant frequency of ETS-related motifs. Combining ChIP-seq data with RNA-seq data allowed us to identify direct MYB target genes. We also compared ChIP-seq data with digital genomic footprinting. MYB is occupying nearly a third of the super-enhancers in K562. Finally, we concluded that MYB cooperates with a subset of the other highly expressed TFs in this cell line, as expected for a master regulator.
Databáze: MEDLINE
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