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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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.

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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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