GFI1
Domain
Zinc fingers 3, 4 and 5 are required for DNA-binding and for interaction with SPI1.
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.
Function
Transcription repressor essential for hematopoiesis (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Functions in a cell-context and development-specific manner (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16287849). Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development (PubMed:12778173). Inhibits SPI1 transcriptional activity at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (By similarity). Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling (By similarity). Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA (PubMed:20547752). Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth (PubMed:19026687). Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters (PubMed:16287849). Required for the maintenance of inner ear hair cells (By similarity). In addition to its role in transcription, acts as a substrate adapter for PRMT1 in the DNA damage response: facilitates the recognition of TP53BP1 and MRE11 substrates by PRMT1, promoting their methylation and the DNA damage response (PubMed:29651020).
Involvement in disease
Neutropenia, severe congenital 2, autosomal dominant
SCN2
A disorder of hematopoiesis characterized by 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Dominant nonimmune chronic idiopathic neutropenia of adults
NI-CINA
Relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated. Ubiquitination and degradation by the proteasome is inhibited by the ubiquitin ligase, ARIH2.
Cellular localization
- Nucleus
- Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.
Alternative names
ZNF163, GFI1, Zinc finger protein Gfi-1, Growth factor independent protein 1, Zinc finger protein 163