Gfi1 Expression Is Controlled by Five Distinct Regulatory Regions Spread over 100 Kilobases, with Scl/Tal1, Gata2, PU.1, Erg, Meis1, and Runx1 Acting as Upstream Regulators in Early Hematopoietic Cells

摘要: The growth factor independence 1 (Gfi1) gene was originally discovered in the hematopoietic system, where it functions as a key regulator of stem cell homeostasis, well neutrophil and T-cell development. Outside blood Gfi1 is essential for inner-ear hair intestinal secretory differentiation. To understand regulatory hierarchies within which operates to control these diverse biological functions, we used combination comparative genomics, locus-wide chromatin immunoprecipitation assays, functional validation lines, extensive transgenic mouse assays identify characterize complete ensemble elements. This concerted effort identified five distinct elements spread over 100kb each driving expression mice subdomain endogenous Gfi1. Detailed characterization an enhancer 35 kb upstream demonstrated activity dorsal aorta region fetal liver mice, bound by transcription factors Scl/Tal1, PU.1/Sfpi1, Runx1, Erg, Meis1, Gata2. Taken together, our results reveal regions responsible importantly establish that at sites (HSC) emergence controlled HSC regulators, thus integrating into wider networks.