Growth factor independent 1 (Gfi-1) is a transcriptional repressor that specifically binds to the DNA consensus sequence TAAATCAC(A/T)GCA. The carboxy-terminus of Gfi-1 contains six C2H2-type zinc finger motifs, and zinc fingers 3, 4 and 5 are required for the binding of Gfi-1 to its DNA binding site. Gfi-1 also contains a 20 amino acid SNAG domain which mediates transcriptional repression. It represses Bax at the mRNA and protein levels, resulting in the inhibition of cell death. Gfi1 is expressed outside the lymphoid system in granulocytes and activated macrophages. Gfi-1B, a related protein, is a transcriptional repressor primarily expressed in bone marrow and spleen. Gfi-1B is a direct repressor of the p21 promoter and the Socs 1 and 3 promoters. The genes encoding human Gfi-1 and Gfi-1B map to chromosome 1p22 and 9q34.3, respectively.
Function: Transcription factor regulating the expression of genes active during S-phase of the cell cycle in hematopoietic cells. Represses ELA2 transcription.
Subunit: Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2 (By similarity). Also interacts with HDAC1. Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via ITS LIM domains); the interaction results in the HDASLCdependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity and represses SPI1-regulated macrophage-specific genes required for proper granulocyte development. Interacts with RUNX1T1; the interaction represses HDASLCmediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response. Interacts (via the SLCterminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKN1B promoters and repression of transcription.
Subcellular Location: Nucleus. Note=Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.
Post-translational modifications: Ubiquitinated.
DISEASE: Defects in GFI1 are a cause of neutropenia severe congenital autosomal dominant type 2 (SCN2) [MIM:613107]. SCN2 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Defects in GFI1 are a cause of dominant nonimmune chronic idiopathic neutropenia of adults (NI-CINA) [MIM:607847]. NI-CINA is a relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.
Sample:
Lung (Mouse) Lysate at 40 ug
Lymph node (Mouse) Lysate at 40 ug
Primary: Anti- GFI1 (SL13337R) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 49 kD
Observed band size: 49 kD