Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB
Abstract 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 l...
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2021-04-01
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doaj-aff4d035089f405cb2b6a55119ff48412021-05-02T11:35:31ZengNature Publishing GroupScientific Reports2045-23222021-04-0111111810.1038/s41598-021-88516-wChromatin occupancy and target genes of the haematopoietic master transcription factor MYBRoza B. Lemma0Marit Ledsaak1Bettina M. Fuglerud2Geir Kjetil Sandve3Ragnhild Eskeland4Odd S. Gabrielsen5Department of Biosciences, University of OsloDepartment of Biosciences, University of OsloDepartment of Biosciences, University of OsloDepartment of Informatics, University of OsloDepartment of Biosciences, University of OsloDepartment of Biosciences, University of OsloAbstract 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.https://doi.org/10.1038/s41598-021-88516-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roza B. Lemma Marit Ledsaak Bettina M. Fuglerud Geir Kjetil Sandve Ragnhild Eskeland Odd S. Gabrielsen |
spellingShingle |
Roza B. Lemma Marit Ledsaak Bettina M. Fuglerud Geir Kjetil Sandve Ragnhild Eskeland Odd S. Gabrielsen Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB Scientific Reports |
author_facet |
Roza B. Lemma Marit Ledsaak Bettina M. Fuglerud Geir Kjetil Sandve Ragnhild Eskeland Odd S. Gabrielsen |
author_sort |
Roza B. Lemma |
title |
Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB |
title_short |
Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB |
title_full |
Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB |
title_fullStr |
Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB |
title_full_unstemmed |
Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB |
title_sort |
chromatin occupancy and target genes of the haematopoietic master transcription factor myb |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-04-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-021-88516-w |
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