GFI1

This gene encodes a nuclear zinc finger protein that functions as a transcriptional repressor. This protein plays a role in diverse developmental contexts, including hematopoiesis and oncogenesis. It functions as part of a complex along with other cofactors to control histone modifications that lead to silencing of the target gene promoters. Mutations in this gene cause autosomal dominant severe congenital neutropenia, and also dominant nonimmune chronic idiopathic neutropenia of adults, which are heterogeneous hematopoietic disorders that cause predispositions to leukemias and infections. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

Full Name

Growth Factor Independent 1 Transcriptional Repressor

Function

Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. 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. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. 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. Required for the maintenance of inner ear hair cells.

Biological Process

Cellular response to lipopolysaccharide Source: UniProtKB
Hemopoiesis Source: InterPro
Negative regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
Negative regulation of neuron projection development Source: UniProtKB
Negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Negative regulation of vitamin D biosynthetic process Source: BHF-UCL
Positive regulation of interleukin-6-mediated signaling pathway Source: UniProtKB
Regulation of histone H3-K4 methylation Source: InterPro
Regulation of toll-like receptor signaling pathway Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Regulation of transcription involved in G1/S transition of mitotic cell cycle Source: ProtInc
Viral process Source: ProtInc

Cellular Location

Nucleus. Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.

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.
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.

PTM

Ubiquitinated. Ubiquitination and degradation by the proteasome is inhibited by the ubiquitin ligase, ARIH2.