Cis-regulatory mechanisms governing stem and progenitor cell transitions
作者： K. D. Johnson , G. Kong , X. Gao , Y.-I. Chang , K. J. Hewitt
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摘要: Cis-element encyclopedias provide information on phenotypic diversity and disease mechanisms. Although cis-element polymorphisms mutations are instructive, deciphering function remains challenging. Mutation of an intronic GATA motif (+9.5) in GATA2, encoding a master regulator hematopoiesis, underlies immunodeficiency associated with myelodysplastic syndrome (MDS) acute myeloid leukemia (AML). Whereas inversion relocalizes another GATA2 (-77) to the proto-oncogene EVI1, inducing EVI1 expression AML, whether this reflects ectopic or physiological activity is unknown. We describe mouse strain that decouples -77 from deregulation. The -77(-/-) mice exhibited novel constellation including late embryonic lethality anemia. established vital sector progenitor transcriptome, conferring multipotentiality. Unlike +9.5(-/-) embryos, hematopoietic stem cell genesis was unaffected embryos. These results illustrate paradigm which cis-elements locus differentially control transitions, therefore individual alterations cause unique overlapping phenotypes.
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