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. Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2) and with RUNX1T1 (By similarity). Forms a complex with GATA1. Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2. Localized at foci of pericentric heterochromatin. Expressed in bone marrow and in spleen. Detected in hematopoietic stem cells, erythroblasts, and megakaryocytes. Expressed in thymocytes. Down-regulated by IL6 treatment in myelomonocytic cells, and in response to EPO in myeloid cells; EPO-induced down-regulation of Gfi1b is STAT5-dependent. The zinc finger domain is essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain. The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors. Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex. Mice are not viable and embryos die by 15 dpc during the transition from primitive to definitive hematopoiesis. They exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce enucleated erythrocytes. Their fetal liver contains erythroid and megakaryocytic precursor arrested in their development. Transgenic mice with insertion of green fluorescence protein (GFP) cDNA in Gfi1b gene allowed to show up-regulation of Gfi1b in early stage of B-cell and in a subset of early thymic pre-T-cell. Mice overexpressing Gfi1b display peripheral T-lymphopenia and a profound defect in activation after CD3 cross-linking. Spleen cells show reduction in the numbers of CD4 and CD8 T-cells. Thymocyte lineage commitment and maturation are altered.