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

Sci Rep. 2021 Apr 26;11(1):9008. doi: 10.1038/s41598-021-88516-w.

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.

MeSH terms

  • Binding Sites*
  • Cell Differentiation / genetics
  • Chromatin / genetics*
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Computational Biology / methods
  • Databases, Genetic
  • Epigenesis, Genetic
  • Epigenomics / methods
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • K562 Cells
  • Models, Biological
  • Nucleotide Motifs
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Transcriptome

Substances

  • Chromatin
  • Proto-Oncogene Proteins c-myb