The family of Gfi-1 zinc finger transcriptional repressor oncoproteins in hematopoiesis regulation Volume 12, issue 6, Novembre-Décembre 2006


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Département d’hématologie, Institut Cochin, INSERM U567, CNRS UMR 8104, Université Paris V, 27, rue du Faubourg Saint-Jacques, 75014 Paris

Gfi-1 and Gfi-1B belong to the family of Gfi-1 zinc finger transcriptional repressor oncoproteins. Gfi-1 and Gfi-1B share a N-terminal transcriptional repressor domain (SNAG) and a nearly identical C-terminal six-zinc finger DNA-binding domain. The expression patterns of Gfi-1 and Gfi-1B within the hematopoietic tissues are highly distinct. Gfi-1 is expressed in stem cells, in neutrophils, in early B and T lymphocytes. Conversely, Gfi-1B is expressed in erythroid and megakaryocytic cells. While inactivation of Gfi-1 gene in mice is not lethal, it leads to many hematopoietic disorders. Indeed, self-renewal and long-term repopulating ability of stem cells are impaired, neutrophil differentiation is abolished and thymic cellularity is reduced. In contrast, Gfi-1B deficient mice die in utero with failure to produce definitive enucleated erythrocytes. While Gfi-1 mutations in zinc finger domain cause human severe neutropenia, no Gfi-1B mutation has been described today. The identification of target genes and interacting cofactors would help to unravel the function of these transcriptional repressor factors in the regulation of hematopoiesis.