Gfil regulates miR- and miR-9b to control myelopoiesis

摘要

The zinc finger protein growth factor independent- (Gfi) is a transcriptional repressor that is critically required for normal granulocytic differentiation. GFI loss-of-function mutations'are found in some patients with severe congenital neu-tropenia (SCN). The SCN-associated GFI-mutant proteins act as dominant negatives to block granulopoiesis through selective deregulation of a subset of GFI target genes. Here we show that Gfi is a master regulator of microRNAs, and thatderegulated expression of these microRNAs recapitulates a Gfi loss-of-function block to granulocyte colony-stimulating factor (G-CSF)-stimulated granulopoiesis. Specifically, bone marrow cells from a GFI -mutant SCN patient and GfH