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Transcriptional networks controlling blood stem cells

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Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks. We have identified a regulatory circuit made up of three genes and their enhancers that operates during specification of blood stem cells in the mouse embryo. The three stem cell enhancers are bound by each of their transcription factors and thus form a fully connected triad. One subcircuit of this network constitutes the first example of any network motif operating during the specification of mammalian stem cells where all the individual components have been identified. We are currently performing quantitative measurements of the regulatory interactions within this subcircuit during the specification of early haematopoietic cells from differentiating embryonic stem cells. Together with experimental information on protein complexes, we are using these new quantitative measurements to build mathematical models for the regulaory subcircuit to develop novel hypotheses for experimental validation

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