Zinc finger protein Gfi-1b

Definition:

Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Transcriptional repressor or activator depending on both promoter and cell type context; represses promoter activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling pathways. Cooperates with GATA1 to repress target gene transcription, such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic cell lines markedly increase apoptosis rate. Inhibits down-regulation of MYC and MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 and GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells. Suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction. Binds to gamma-satellite DNA and to its own promoter, auto-repressing its own expression. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation.

References:

[1]. Yuan-Yeh Kuo, et al. GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription. Mol Cell Biol. 2007 Jun;27(12):4261-72. [Content Brief]

[2]. Duen-Yi Huang, et al. GATA-1 mediates auto-regulation of Gfi-1B transcription in K562 cells. Nucleic Acids Res. 2005 Sep 21;33(16):5331-42. [Content Brief]

[3]. Wei Xu, et al. Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas. Blood. 2007 May 15;109(10):4406-14. [Content Brief]

[4]. Mitsujiro Osawa, et al. Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis. Blood. 2002 Oct 15;100(8):2769-77. [Content Brief]

[5]. Lothar Vassen, et al. Gfi1b alters histone methylation at target gene promoters and sites of gamma-satellite containing heterochromatin. EMBO J. 2006 Jun 7;25(11):2409-19. [Content Brief]

[6]. Ruth Schwartz, et al. Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9976-81. [Content Brief]

[7]. Ahmet H Elmaagacli, et al. Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate. Br J Haematol. 2007 Jan;136(2):212-9. [Content Brief]

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