Gfi-1 Oncoproteins in Hematopoiesis

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.

Keywords:

• Gfi-1
• Gfi-1B
• Hematopoiesis
• Neutropenia
• Lymphopenia