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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Autores principales:	Roza B. Lemma, Marit Ledsaak, Bettina M. Fuglerud, Geir Kjetil Sandve, Ragnhild Eskeland, Odd S. Gabrielsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aff4d035089f405cb2b6a55119ff4841
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spelling	oai:doaj.org-article:aff4d035089f405cb2b6a55119ff48412021-12-02T17:20:12ZChromatin occupancy and target genes of the haematopoietic master transcription factor MYB10.1038/s41598-021-88516-w2045-2322https://doaj.org/article/aff4d035089f405cb2b6a55119ff48412021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88516-whttps://doaj.org/toc/2045-2322Abstract 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.Roza B. LemmaMarit LedsaakBettina M. FuglerudGeir Kjetil SandveRagnhild EskelandOdd S. GabrielsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Roza B. Lemma Marit Ledsaak Bettina M. Fuglerud Geir Kjetil Sandve Ragnhild Eskeland Odd S. Gabrielsen
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 Portfolio
publishDate	2021
url	https://doaj.org/article/aff4d035089f405cb2b6a55119ff4841
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Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB

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