title: Identification of c-Myb Target Genes in K562 Cells Reveals a Role for c-Myb as a Master Regulator.
abstract: The c-Myb transcription factor is an important regulator of hematopoietic cell development. c-Myb is expressed in immature hematopoietic cells and plays a direct role in lineage fate selection, cell cycle progression, and differentiation of myeloid as well as B- and T-lymphoid progenitor cells. As a DNA-binding transcription factor, c-Myb regulates specific gene programs through activation of target genes. Still, our understanding of these programs is incomplete. Here, we report a set of novel c-Myb target genes, identified using a combined approach: specific c-Myb knockdown by 2 different siRNAs and subsequent global expression profiling, combined with the confirmation of direct binding of c-Myb to the target promoters by ChIP assays. The combination of these 2 approaches, as well as additional validation such as cloning and testing the promoters in reporter assays, confirmed that MYADM, LMO2, GATA2, STAT5A, and IKZF1 are target genes of c-Myb. Additional studies, using chromosome conformation capture, demonstrated that c-Myb target genes may directly interact with each other, indicating that these genes may be coordinately regulated. Of the 5 novel target genes identified, 3 are transcription factors, and one is a transcriptional co-regulator, supporting a role of c-Myb as a master regulator controlling the expression of other transcriptional regulators in the hematopoietic system.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Petra Isabel
authors.initials: PI
authors.lastname: Lorenzo
authors.forename: Elen Margrethe
authors.initials: EM
authors.lastname: Brendeford
authors.forename: Siv
authors.initials: S
authors.lastname: Gilfillan
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Gavrilov
authors.forename: Marit
authors.initials: M
authors.lastname: Leedsak
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Razin
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Eskeland
authors.forename: Thomas
authors.initials: T
authors.lastname: Sæther
authors.forename: Odd Stokke
authors.initials: OS
authors.lastname: Gabrielsen