Zinc finger protein Gfi-1

Definition:

Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Inhibits SPI1 transcriptional activity at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (By similarity). Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters. Required for the maintenance of inner ear hair cells.

References:

[1]. Q Liu, et al. A role of Miz-1 in Gfi-1-mediated transcriptional repression of CDKN1A. Oncogene. 2010 May 13;29(19):2843-52. [Content Brief]

[2]. Richard E Person, et al. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat Genet. 2003 Jul;34(3):308-12. [Content Brief]

[3]. Suchitra Basu, et al. Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1433-8. [Content Brief]

[4]. Jurgen A F Marteijn, et al. Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1. Blood. 2007 Nov 1;110(9):3128-35. [Content Brief]

[5]. B Rödel, et al. The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3. EMBO J. 2000 Nov 1;19(21):5845-55. [Content Brief]

[6]. Richard Dahl, et al. The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein-protein interaction. J Biol Chem. 2007 Mar 2;282(9):6473-83. [Content Brief]

[7]. P A Zweidler-Mckay, et al. Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor. Mol Cell Biol. 1996 Aug;16(8):4024-34. [Content Brief]

[8]. Zhijun Duan, et al. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Mol Cell Biol. 2005 Dec;25(23):10338-51. [Content Brief]

[9]. Ehssan Sharif-Askari, et al. Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65. Mol Cell Biol. 2010 Aug;30(16):3929-42. [Content Brief]

[10]. Valeria S Ossovskaya, et al. Loss of function genetic screens reveal MTGR1 as an intracellular repressor of beta1 integrin-dependent neurite outgrowth. J Neurosci Methods. 2009 Mar 15;177(2):322-33. [Content Brief]

[11]. Diego E Montoya-Durango, et al. Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor. J Biol Chem. 2008 Nov 14;283(46):32056-65. [Content Brief]

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