Biology:GFI1
 Generic protein structure example |
Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the GFI1 gene.[1] It is important normal hematopoiesis.[2]
Function
Gfi1 (growth factor independence 1) is a transcriptional repressor that plays a critical role in hematopoiesis and in protecting hematopoietic cells against stress-induced apoptosis. Gfi1 upregulates the expression of the nuclear protein Hemgn, which contributes to its anti-apoptotic activity. This upregulation is mediated through a specific 16-bp promoter region and is dependent on Gfi1’s interaction with the histone demethylase LSD1.[3] Gfi1 represses PU.1 transcription factor, and this repression precedes and correlates with the upregulation of Hemgn. The upregulation of Hemgn, in turn, contributes to the anti-apoptotic function of Gfi1, acting in a p53-independent manner.[3][4]
Gfi1 promotes cell survival by upregulating Hemgn through the repression of PU.1 thereby inhibiting apoptosis.[3] Gfi1 inhibits apoptosis induced by DNA damage, growth factor withdrawal, inhibitory cytokine TGF-β and MYC activation [4]
Gfi1 is also expressed in the inner ear, and in the epithelium lining the stomach, intestines, and lung airways, where it is important for cellular differentiation.[5][6]
In lymphoid lineages, GFI1 plays a vital role in directing cell fate decisions, differentiation and functional maintenance. Within CD8+ T cells, GFI1-driven transcriptional and epigenetic programs are essential for preserving cellular stemness and long-term persistence.[7] [8] Beyond the T cell lineage, the GFI1–FOXO1 axis functions as a key regulator of natural killer (NK) cell maturation and effector function. [9]
Interactions
GFI1 has been shown to interact with PIAS3[10] and RUNX1T1.[11]
References
- ↑ "Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents". Cytogenetics and Cell Genetics 70 (3–4): 263–267. July 1995. doi:10.1159/000134048. PMID 7789186.
- ↑ "Entrez Gene: GFI1 growth factor independent 1". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2672.
- ↑ 3.0 3.1 3.2 "Upregulation of nuclear protein Hemgn by transcriptional repressor Gfi1 through repressing PU.1 contributes to the anti-apoptotic activity of Gfi1". The Journal of Biological Chemistry 300 (11). November 2024. doi:10.1016/j.jbc.2024.107860. PMID 39374784. Bibcode: 2024JBiCh.300j7860G.
- ↑ 4.0 4.1 "Bcl-xL is important for the antiapoptotic activity of Gfi1 and is upregulated by Gfi1 through hemgn". Journal of Immunology (Baltimore, Md.) 214 (5): 1046–1058. May 2025. doi:10.1093/jimmun/vkae066. PMID 40262274.
- ↑ "Gfi1-cells and circuits: unraveling transcriptional networks of development and disease". Current Opinion in Hematology 17 (4): 300–307. July 2010. doi:10.1097/moh.0b013e32833a06f8. PMID 20571393.
- ↑ "Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation". Genes & Development 19 (20): 2412–2417. October 2005. doi:10.1101/gad.1353905. PMID 16230531.
- ↑ "GFI1-driven transcriptional and epigenetic programs maintain CD8+ T cell stemness and persistence". Nature Immunology 26: 894–907. 2025. doi:10.1038/s41590-025-02151-5.
- ↑ "Transcriptional programming governs the transition from shared progenitors to divergent CD8(+) T cell fates". Immunology & Cell Biology 104: 396–399. 2026. doi:10.1111/imcb.70101.
- ↑ "The GFI1–FOXO1 axis regulates NK cell maturation and function". Nature Communications 17. 2026. doi:10.1038/s41467-026-72022-6.
- ↑ "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal 19 (21): 5845–5855. November 2000. doi:10.1093/emboj/19.21.5845. PMID 11060035.
- ↑ "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism". Journal of Cellular Biochemistry 89 (5): 1005–1018. August 2003. doi:10.1002/jcb.10548. PMID 12874834.
Further reading
- "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". Molecular and Cellular Biology 13 (3): 1759–1768. March 1993. doi:10.1128/MCB.13.3.1759. PMID 8441411.
- "Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor". Molecular and Cellular Biology 16 (8): 4024–4034. August 1996. doi:10.1128/MCB.16.8.4024. PMID 8754800.
- "Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22". Oncogene 14 (8): 1003–1005. February 1997. doi:10.1038/sj.onc.1200910. PMID 9051000.
- "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal 19 (21): 5845–5855. November 2000. doi:10.1093/emboj/19.21.5845. PMID 11060035.
- "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis". Blood 100 (8): 2769–2777. October 2002. doi:10.1182/blood-2002-01-0182. PMID 12351384.
- "Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2". Nature Genetics 34 (3): 308–312. July 2003. doi:10.1038/ng1170. PMID 12778173.
- "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism". Journal of Cellular Biochemistry 89 (5): 1005–1018. August 2003. doi:10.1002/jcb.10548. PMID 12874834.
- "Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells". Nucleic Acids Research 32 (8): 2508–2519. 2004. doi:10.1093/nar/gkh570. PMID 15131254.
- "Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells". Endocrine-Related Cancer 12 (2): 351–365. June 2005. doi:10.1677/erc.1.00920. PMID 15947108.
- "Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1". Molecular and Cellular Biology 25 (23): 10338–10351. December 2005. doi:10.1128/MCB.25.23.10338-10351.2005. PMID 16287849.
- "Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes". Blood 109 (1): 100–108. January 2007. doi:10.1182/blood-2006-02-003590. PMID 16888099.
- "Role of oncoprotein growth factor independent-1 (GFI1) in repression of 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1): a comparative analysis in human prostate cancer and kidney cells". The Journal of Steroid Biochemistry and Molecular Biology 103 (3–5): 742–746. March 2007. doi:10.1016/j.jsbmb.2006.12.014. PMID 17207994.
- "Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression". Oncogene 26 (24): 3541–3550. May 2007. doi:10.1038/sj.onc.1210140. PMID 17213822.
- "Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPϵ gene". Blood 109 (10): 4181–4190. May 2007. doi:10.1182/blood-2005-05-022004. PMID 17244686.
- "Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1". Blood 110 (9): 3128–3135. November 2007. doi:10.1182/blood-2006-11-058602. PMID 17646546.
External links
- GFI1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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