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Gene Review

GFI1  -  growth factor independent 1 transcription...

Homo sapiens

Synonyms: GFI-1, GFI1A, Growth factor independent protein 1, SCN2, ZNF163, ...
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Disease relevance of GFI1


High impact information on GFI1

  • We show by chromatin immunoprecipitation, gel shift, reporter assays and elevated expression of ELA2 in vivo in neutropenic individuals that GFI1 represses ELA2, linking these two genes in a common pathway involved in myeloid differentiation [1].
  • Here, we present experimental evidence implementing the zinc finger protein Gfi-1 as a new regulatory factor in STAT3-mediated signal transduction [5].
  • Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes [6].
  • Conversely, Gfi1 mRNA levels are high in granulocytes but the protein is swiftly degraded by the proteasome in these cells [6].
  • Gfi1(-/-) mice exhibit a block in myeloid differentiation resulting in the accumulation of an immature myelo-monocytic cell population and the complete absence of mature neutrophils [6].

Chemical compound and disease context of GFI1


Biological context of GFI1

  • We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref. 3). We found dominant negative zinc finger mutations that disable transcriptional repressor activity [1].
  • GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation [7].
  • Importantly, GFI1 repression is dependent on an intact GFI1 binding site in the -997 to -1200 region [2].
  • These studies demonstrate that GFI1 may play a significant role in the down regulation of endogenous production of 1,25D in prostate cancer cells and could provide a novel insight to future diagnosis and treatment [8].
  • These EM(CD45RA+) IL-7Ralphalow cells were largely antigen experienced (CD27-CD28-), replicatively senescent (CD57+), and perforinhigh CD8+ T cells that had decreased IL-7Ralpha mRNA, independent of guanine and adenine binding protein alpha (GABPalpha) and growth factor independence-1 (GFI1) expression [9].

Anatomical context of GFI1


Associations of GFI1 with chemical compounds


Physical interactions of GFI1


Regulatory relationships of GFI1


Other interactions of GFI1

  • Endogenous Gfi1 colocalizes with G9a, HDAC1, and K9-dimethylated histone H3 [10].


  1. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Person, R.E., Li, F.Q., Duan, Z., Benson, K.F., Wechsler, J., Papadaki, H.A., Eliopoulos, G., Kaufman, C., Bertolone, S.J., Nakamoto, B., Papayannopoulou, T., Grimes, H.L., Horwitz, M. Nat. Genet. (2003) [Pubmed]
  2. 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. Dwivedi, P.P., Anderson, P.H., Omdahl, J.L., Grimes, H.L., Morris, H.A., May, B.K. Endocr. Relat. Cancer (2005) [Pubmed]
  3. Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells. Kazanjian, A., Wallis, D., Au, N., Nigam, R., Venken, K.J., Cagle, P.T., Dickey, B.F., Bellen, H.J., Gilks, C.B., Grimes, H.L. Cancer Res. (2004) [Pubmed]
  4. Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line. Bagnarelli, P., Devescovi, G., Manzin, A., Bearzi, I., Bonazzi, P., Carloni, G., Clementi, M. Hepatology (1990) [Pubmed]
  5. The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3. Rödel, B., Tavassoli, K., Karsunky, H., Schmidt, T., Bachmann, M., Schaper, F., Heinrich, P., Shuai, K., Elsässer, H.P., Möröy, T. EMBO J. (2000) [Pubmed]
  6. Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes. Marteijn, J.A., van der Meer, L.T., Van Emst, L., de Witte, T., Jansen, J.H., van der Reijden, B.A. Blood (2007) [Pubmed]
  7. Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Doan, L.L., Porter, S.D., Duan, Z., Flubacher, M.M., Montoya, D., Tsichlis, P.N., Horwitz, M., Gilks, C.B., Grimes, H.L. Nucleic Acids Res. (2004) [Pubmed]
  8. 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. Dwivedi, P.P., Anderson, P.H., Tilley, W.D., May, B.K., Morris, H.A. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  9. Altered IL-7Ralpha expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses. Kim, H.R., Hong, M.S., Dan, J.M., Kang, I. Blood (2006) [Pubmed]
  10. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H.L., Horwitz, M. Mol. Cell. Biol. (2005) [Pubmed]
  11. Growth factor-independent activation of protein kinase B contributes to the inherent resistance of vascular endothelium to radiation-induced apoptotic response. Tan, J., Hallahan, D.E. Cancer Res. (2003) [Pubmed]
  12. An increase in the expression and total activity of endogenous p60(c-Src) in several factor-independent mutants of a human GM-CSF-dependent leukemia cell line (TF-1). Horn, S., Meyer, J., Stocking, C., Ostertag, W., Jücker, M. Oncogene (2003) [Pubmed]
  13. Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1. Marteijn, J.A., van der Meer, L.T., van Emst, L., van Reijmersdal, S., Wissink, W., de Witte, T., Jansen, J.H., Van der Reijden, B.A. Blood (2007) [Pubmed]
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