Gfi-1 Oncoproteins in Hematopoiesis

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Abstract
The family of Gfi-1 zinc finger transcriptional repressor oncoproteins consists of Gfi-1 and Gfi-1B. Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis. Mice lacking Gfi-1 are unexpectedly neutropenic. Neutrophil differentiation is abolished and T lymphocyte differentiation is partially blocked in these mice. Heterozygous germline mutations of Gfi-1 causes severe congenital neutropenia (SCN) in humans. Ela2, whose germline mutation is the major contributor to hereditary neutropenias, is repressed in vivo by Gfi-1. Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development. The ongoing identification of repressed target genes and interacting transcriptional cofactors is helping to unravel the central contributions of these two hematopoietic factors.