GFI1

GFI1
Identifiers
Aliases	GFI1 , GFI-1, GFI1A, SCN2, ZNF163, growth factor independent 1 transcriptional repressor
External IDs	OMIM: 600871; MGI: 103170; HomoloGene: 3854; GeneCards: GFI1; OMA:GFI1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p22.1 Start 92,473,043 bp [1] End 92,486,925 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5 F|5 52.23 cM Start 107,864,523 bp [2] End 107,873,902 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte bone marrow bone marrow cell trabecular bone body of pancreas testicle thymus blood lymph node spleen Top expressed in utricle vestibular sensory epithelium thymus saccule granulocyte spermatocyte bone marrow tongue mesenteric lymph nodes embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding metal ion binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity Cellular component nuclear body nuclear matrix transcription repressor complex nucleus nucleoplasm Biological process positive regulation of interleukin-6-mediated signaling pathway negative regulation of neuron projection development regulation of transcription, DNA-templated regulation of toll-like receptor signaling pathway regulation of histone H3-K4 methylation negative regulation of transcription by RNA polymerase II regulation of transcription involved in G1/S transition of mitotic cell cycle transcription, DNA-templated negative regulation of vitamin D biosynthetic process negative regulation of calcidiol 1-monooxygenase activity viral process negative regulation of transcription, DNA-templated negative regulation of NF-kappaB transcription factor activity cellular response to lipopolysaccharide hemopoiesis positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2672 14581 Ensembl ENSG00000162676 ENSMUSG00000029275 UniProt Q99684 P70338 RefSeq (mRNA) NM_001127215 NM_001127216 NM_005263 NM_001267621 NM_010278 RefSeq (protein) NP_001120687 NP_001120688 NP_005254 NP_001254550 NP_034408 Location (UCSC) Chr 1: 92.47 – 92.49 Mb Chr 5: 107.86 – 107.87 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the GFI1 gene. ^[5] It is important normal hematopoiesis. ^[6]

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. ^[7] 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. ^{[7] [8]}

Gfi1 promotes cell survival by upregulating Hemgn through the repression of PU.1 thereby inhibiting apoptosis. ^[7] Gfi1 inhibits apoptosis induced by DNA damage, growth factor withdrawal, inhibitory cytokine TGF-β and MYC activation ^[8]

Interactions

GFI1 has been shown to interact with PIAS3 ^[9] and RUNX1T1. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000162676 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029275 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bell DW, Taguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Gilks CB, et al. (July 1995). "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. doi:10.1159/000134048. PMID   7789186.
6. "Entrez Gene: GFI1 growth factor independent 1".
7. Binod GC, Hoyt LJ, Dovat S, Dong F (November 2024). "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) 107860. Bibcode:2024JBiCh.300j7860G. doi: 10.1016/j.jbc.2024.107860 . PMC   11550643 . PMID   39374784.
8. Binod GC, Du P, Zhang Y, Yang L, Dong F (May 2025). "Bcl-xL is important for the antiapoptotic activity of Gfi1 and is upregulated by Gfi1 through hemgn". Journal of Immunology. 214 (5). Baltimore, Md.: 1046–1058. doi:10.1093/jimmun/vkae066. PMC  12123215. PMID   40262274.
9. Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, et al. (November 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal. 19 (21): 5845–5855. doi:10.1093/emboj/19.21.5845. PMC   305799 . PMID   11060035.
10. McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, et al. (August 2003). "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. doi:10.1002/jcb.10548. PMID   12874834. S2CID   25450754.

Further reading

• Gilks CB, Bear SE, Grimes HL, Tsichlis PN (Mar 1993). "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. doi:10.1128/MCB.13.3.1759. PMC   359488 . PMID   8441411.
• Zweidler-Mckay PA, Grimes HL, Flubacher MM, Tsichlis PN (Aug 1996). "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. doi:10.1128/MCB.16.8.4024. PMC   231398 . PMID   8754800.
• Roberts T, Cowell JK (Feb 1997). "Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22". Oncogene. 14 (8): 1003–1005. doi: 10.1038/sj.onc.1200910 . PMID   9051000.
• Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, et al. (Nov 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal. 19 (21): 5845–5855. doi:10.1093/emboj/19.21.5845. PMC   305799 . PMID   11060035.
• Osawa M, Yamaguchi T, Nakamura Y, Kaneko S, Onodera M, Sawada K, et al. (Oct 2002). "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis". Blood. 100 (8): 2769–2777. doi:10.1182/blood-2002-01-0182. PMID   12351384.
• Person RE, Li FQ, Duan Z, Benson KF, Wechsler J, Papadaki HA, et al. (Jul 2003). "Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2". Nature Genetics. 34 (3): 308–312. doi:10.1038/ng1170. PMC   2832179 . PMID   12778173.
• McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, et al. (Aug 2003). "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. doi:10.1002/jcb.10548. PMID   12874834. S2CID   25450754.
• Doan LL, Porter SD, Duan Z, Flubacher MM, Montoya D, Tsichlis PN, et al. (2004). "Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells". Nucleic Acids Research. 32 (8): 2508–2519. doi:10.1093/nar/gkh570. PMC   419458 . PMID   15131254.
• Dwivedi PP, Anderson PH, Omdahl JL, Grimes HL, Morris HA, May BK (Jun 2005). "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. doi: 10.1677/erc.1.00920 . PMID   15947108.
• Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M (Dec 2005). "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. doi:10.1128/MCB.25.23.10338-10351.2005. PMC   1291230 . PMID   16287849.
• Marteijn JA, van der Meer LT, Van Emst L, de Witte T, Jansen JH, van der Reijden BA (Jan 2007). "Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes". Blood. 109 (1): 100–108. doi: 10.1182/blood-2006-02-003590 . PMID   16888099.
• Dwivedi PP, Anderson PH, Tilley WD, May BK, Morris HA (Mar 2007). "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. doi:10.1016/j.jsbmb.2006.12.014. PMID   17207994. S2CID   30600875.
• Nakazawa Y, Suzuki M, Manabe N, Yamada T, Kihara-Negishi F, Sakurai T, et al. (May 2007). "Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression". Oncogene. 26 (24): 3541–3550. doi:10.1038/sj.onc.1210140. PMID   17213822. S2CID   30476328.
• Khanna-Gupta A, Sun H, Zibello T, Lee HM, Dahl R, Boxer LA, et al. (May 2007). "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. doi:10.1182/blood-2005-05-022004. PMC   1885490 . PMID   17244686.
• Marteijn JA, van der Meer LT, van Emst L, van Reijmersdal S, Wissink W, de Witte T, et al. (Nov 2007). "Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1". Blood. 110 (9): 3128–3135. doi:10.1182/blood-2006-11-058602. PMID   17646546. S2CID   19048016.

External links

• GFI1+protein,+human at the U.S. 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.