GFI1 explained

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] 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 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.^[3]

Interactions

GFI1 has been shown to interact with PIAS3^[4] and RUNX1T1.^[5]

References

Further reading

• Gilks CB, Bear SE, Grimes HL, Tsichlis PN . 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 . 1993 . 8441411 . 359488 . 10.1128/MCB.13.3.1759.
• Zweidler-Mckay PA, Grimes HL, Flubacher MM, Tsichlis PN . Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor . Mol. Cell. Biol. . 16 . 8 . 4024–34 . 1996 . 8754800 . 231398 . 10.1128/MCB.16.8.4024.
• Roberts T, Cowell JK . Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22 . Oncogene . 14 . 8 . 1003–5 . 1997 . 9051000 . 10.1038/sj.onc.1200910 . free .
• Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T . The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3 . EMBO J. . 19 . 21 . 5845–55 . 2000 . 11060035 . 305799 . 10.1093/emboj/19.21.5845 .
• Osawa M, Yamaguchi T, Nakamura Y, Kaneko S, Onodera M, Sawada K, Jegalian A, Wu H, Nakauchi H, Iwama A . Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis . Blood . 100 . 8 . 2769–77 . 2002 . 12351384 . 10.1182/blood-2002-01-0182 .
• 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 . 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 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• 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 . Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2 . Nat. Genet. . 34 . 3 . 308–12 . 2003 . 12778173 . 2832179 . 10.1038/ng1170 .
• McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, Meyers S . 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 . 2003 . 12874834 . 10.1002/jcb.10548 . 25450754 .
• Doan LL, Porter SD, Duan Z, Flubacher MM, Montoya D, Tsichlis PN, Horwitz M, Gilks CB, Grimes HL . Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells . Nucleic Acids Res. . 32 . 8 . 2508–19 . 2004 . 15131254 . 419458 . 10.1093/nar/gkh570 .
• Dwivedi PP, Anderson PH, Omdahl JL, Grimes HL, Morris HA, May BK . 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 . 2005 . 15947108 . 10.1677/erc.1.00920 . free .
• Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M . 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 . 2005 . 16287849 . 1291230 . 10.1128/MCB.25.23.10338-10351.2005 .
• Marteijn JA, van der Meer LT, Van Emst L, de Witte T, Jansen JH, van der Reijden BA . Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes . Blood . 109 . 1 . 100–8 . 2007 . 16888099 . 10.1182/blood-2006-02-003590 . free .
• Dwivedi PP, Anderson PH, Tilley WD, May BK, Morris HA . 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 . 2007 . 17207994 . 10.1016/j.jsbmb.2006.12.014 . 30600875 .
• Nakazawa Y, Suzuki M, Manabe N, Yamada T, Kihara-Negishi F, Sakurai T, Tenen DG, Iwama A, Mochizuki M, Oikawa T . Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression . Oncogene . 26 . 24 . 3541–50 . 2007 . 17213822 . 10.1038/sj.onc.1210140 . 30476328 .
• Khanna-Gupta A, Sun H, Zibello T, Lee HM, Dahl R, Boxer LA, Berliner N . 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 . 2007 . 17244686 . 1885490 . 10.1182/blood-2005-05-022004 .
• Marteijn JA, van der Meer LT, van Emst L, van Reijmersdal S, Wissink W, de Witte T, Jansen JH, Van der Reijden BA . Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1 . Blood . 110 . 9 . 3128–35 . 2007 . 17646546 . 10.1182/blood-2006-11-058602 . 19048016 .

Notes and References

1. Bell DW, Taguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Gilks CB, Zweidler-McKay P, Grimes HL, Tsichlis PN, Testa JR . Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents . Cytogenet Cell Genet . 70 . 3–4 . 263–7 . July 1995 . 7789186 . 10.1159/000134048 .
2. Web site: Entrez Gene: GFI1 growth factor independent 1.
3. G C . Binod . Hoyt . Laney Jia . Dovat . Sinisa . Dong . Fan . Upregulation of nuclear protein Hemgn by transcriptional repressor Gfi1 through repressing PU.1 contributes to the anti-apoptotic activity of Gfi1 . Journal of Biological Chemistry . 300 . 11 . 2024 . 107860 . 10.1016/j.jbc.2024.107860 . free . 39374784 . 11550643 .
4. Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T . The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3 . EMBO J. . 19 . 21 . 5845–55 . November 2000 . 11060035 . 305799 . 10.1093/emboj/19.21.5845 .
5. McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, Meyers S . 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 . August 2003 . 12874834 . 10.1002/jcb.10548 . 25450754 .