Disease relevance of Gfi1

• Gfi-1 is a zinc finger transcriptional repressor originally recognized for its role in T cell differentiation and lymphomas [1].
• Recent experiments reveal that gene-targeted Gfi-1-deficient mice are neutropenic and that Gfi-1 mutations cause human neutropenia [1].
• Expression of Gfi-1 in 2780d cells following transfer of a Gfi-1/LXSN retrovirus construct contributes to the emergence of the IL-2i phenotype [2].
• Gfi-1 is expressed at low levels in IL-2d cell lines cultured in IL-2-containing medium and at high levels in most IL-2i cell lines, including the two harboring a provirus at this locus [2].

High impact information on Gfi1

• We identified 32 Gfi-1 binding sites in a functionally variable set of 16 genes, including complements of cell-cycle regulators, transcription factors, and granulocyte-specific markers [1].
• To identify Gfi-1 targets in vivo, we performed large-scale chromatin immunoprecipitation analysis on a set of 34 candidate genes in myeloblast (KG-1 and HL-60), monoblast (U937), and T lymphocyte cell lines (Jurkat), in concert with RT-PCR-based expression profiling [1].
• Cluster analysis of expression patterns and chromatin immunoprecipitation data reveals that Gfi-1 targets a subset of genes differentiating hematopoietic lineages and therefore plays a relatively superior role in the hierarchy of factors governing stem cell differentiation [1].
• Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis [2].
• Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein [2].

Biological context of Gfi1

• In mitogen-stimulated splenocytes, Gfi-1 expression begins to rise at 12 h after stimulation and reaches very high levels after 50 h, suggesting that it may be functionally involved in events occurring after the interaction of IL-2 with its receptor, perhaps during the transition from the G1 to the S phase of the cell cycle [2].
• Addition of PRL to such stationary cells led to induction of Gfi-1 gene expression within a few hr with a maximum in late G1 [3].
• In the present study, a novel, 14p22 zinc finger protein-encoding gene, Gfi-1, has been examined for a role in Nb2 cell proliferation [3].

Other interactions of Gfi1

• Prolactin (PRL)-dependent expression of a zinc finger protein-encoding gene, Gfi-1, in Nb2 lymphoma cells: constitutive expression in autonomous sublines [3].

References