GFI1

Zinc finger protein Gfi-1 is a transcriptional repressor that in humans is encoded by the GFI1 gene. It is important normal hematopoiesis. 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. Recent research has shown that 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.

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) Band 1p22.1 Start 92,473,043 bp End 92,486,925 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 F|5 52.23 cM Start 107,864,523 bp End 107,873,902 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte bone marrow bone marrow cells 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
Wikidata
View/Edit Human View/Edit Mouse

Gfi1 represses PU.1, 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.

These findings suggest that Gfi1 promotes cell survival by upregulating Hemgn through the repression of PU.1, offering a new understanding of its role in apoptosis regulation.

Interactions

GFI1 has been shown to interact with PIAS3 and RUNX1T1.

Further reading

• Gilks CB, Bear SE, Grimes HL, Tsichlis PN (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". Mol. Cell. Biol. 13 (3): 1759–68. doi:10.1128/MCB.13.3.1759. PMC 359488. PMID 8441411.
• Zweidler-Mckay PA, Grimes HL, Flubacher MM, Tsichlis PN (1996). "Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor". Mol. Cell. Biol. 16 (8): 4024–34. doi:10.1128/MCB.16.8.4024. PMC 231398. PMID 8754800.
• Roberts T, Cowell JK (1997). "Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22". Oncogene. 14 (8): 1003–5. doi:10.1038/sj.onc.1200910. PMID 9051000.
• Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T (2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". EMBO J. 19 (21): 5845–55. doi:10.1093/emboj/19.21.5845. PMC 305799. PMID 11060035.
• Osawa M, Yamaguchi T, Nakamura Y, Kaneko S, Onodera M, Sawada K, Jegalian A, Wu H, Nakauchi H, Iwama A (2002). "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis". Blood. 100 (8): 2769–77. doi:10.1182/blood-2002-01-0182. PMID 12351384.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Person RE, Li FQ, Duan Z, Benson KF, Wechsler J, Papadaki HA, Eliopoulos G, Kaufman C, Bertolone SJ, Nakamoto B, Papayannopoulou T, Grimes HL, Horwitz M (2003). "Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2". Nat. Genet. 34 (3): 308–12. doi:10.1038/ng1170. PMC 2832179. PMID 12778173.
• McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, Meyers S (2003). "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism". J. Cell. Biochem. 89 (5): 1005–18. doi:10.1002/jcb.10548. PMID 12874834. S2CID 25450754.
• Doan LL, Porter SD, Duan Z, Flubacher MM, Montoya D, Tsichlis PN, Horwitz M, Gilks CB, Grimes HL (2004). "Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells". Nucleic Acids Res. 32 (8): 2508–19. doi:10.1093/nar/gkh570. PMC 419458. PMID 15131254.
• Dwivedi PP, Anderson PH, Omdahl JL, Grimes HL, Morris HA, May BK (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". Endocr. Relat. Cancer. 12 (2): 351–65. doi:10.1677/erc.1.00920. PMID 15947108.
• Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M (2005). "Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1". Mol. Cell. Biol. 25 (23): 10338–51. 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 (2007). "Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes". Blood. 109 (1): 100–8. doi:10.1182/blood-2006-02-003590. PMID 16888099.
• Dwivedi PP, Anderson PH, Tilley WD, May BK, Morris HA (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". J. Steroid Biochem. Mol. Biol. 103 (3–5): 742–6. 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, Tenen DG, Iwama A, Mochizuki M, Oikawa T (2007). "Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression". Oncogene. 26 (24): 3541–50. doi:10.1038/sj.onc.1210140. PMID 17213822. S2CID 30476328.
• Khanna-Gupta A, Sun H, Zibello T, Lee HM, Dahl R, Boxer LA, Berliner N (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): 4181–90. 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, Jansen JH, Van der Reijden BA (2007). "Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1". Blood. 110 (9): 3128–35. 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.