Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators - PubMed (original) (raw)
. 2010 Oct 8;7(4):532-44.
doi: 10.1016/j.stem.2010.07.016.
Samuel D Foster, Xiaonan Wang, Kathy Knezevic, Judith Schütte, Polynikis Kaimakis, Paulina M Chilarska, Sarah Kinston, Willem H Ouwehand, Elaine Dzierzak, John E Pimanda, Marella F T R de Bruijn, Berthold Göttgens
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- PMID: 20887958
- DOI: 10.1016/j.stem.2010.07.016
Free article
Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators
Nicola K Wilson et al. Cell Stem Cell. 2010.
Free article
Abstract
Combinatorial transcription factor (TF) interactions control cellular phenotypes and, therefore, underpin stem cell formation, maintenance, and differentiation. Here, we report the genome-wide binding patterns and combinatorial interactions for ten key regulators of blood stem/progenitor cells (SCL/TAL1, LYL1, LMO2, GATA2, RUNX1, MEIS1, PU.1, ERG, FLI-1, and GFI1B), thus providing the most comprehensive TF data set for any adult stem/progenitor cell type to date. Genome-wide computational analysis of complex binding patterns, followed by functional validation, revealed the following: first, a previously unrecognized combinatorial interaction between a heptad of TFs (SCL, LYL1, LMO2, GATA2, RUNX1, ERG, and FLI-1). Second, we implicate direct protein-protein interactions between four key regulators (RUNX1, GATA2, SCL, and ERG) in stabilizing complex binding to DNA. Third, Runx1(+/-)::Gata2(+/-) compound heterozygous mice are not viable with severe hematopoietic defects at midgestation. Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells.
Copyright © 2010 Elsevier Inc. All rights reserved.
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