Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b

Vaßen, Lothar

doi:10.1093/nar/gki243

Cited by 71 publications

(106 citation statements)

References 30 publications

(63 reference statements)

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“…In many hematopoietic subsets, the expression of the Gfi1 and Gfi1b genes can be autoregulated by the Gfi1 and Gfi1b proteins themselves. [13][14][15] Gfi1 may control the expression of the Gfi1b gene and vice versa, [16][17][18] although the biological relevance of this crossregulation is poorly understood as both proteins are expressed in certain cell types. Gfi1 and Gfi1b gene expression is co-regulated by other transcription factors such as Ajuba 19 and Ikaros 20 for Gfi1 and GATA1, NF-Y, Oct1 and HMGB2 for Gfi1b.…”

Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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Transcription factor Growth factor independence 1 (Gfi1) is required for multilineage blood cell development, from stem and progenitor cells to differentiated lymphoid and myeloid cells. Gfi1 expression is rapidly induced by cytokines that control both the adaptive and innate immune systems. Gfi1 itself represses the expression of genes implicated in cell survival, proliferation and differentiation. Changes in Gfi1 expression and function have not only been implicated in neutropenia, allergy, autoimmunity and hyperinflammatory responses, but also in lymphoma and more recently in the development of leukemia. In this study, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.

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Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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“…Mice were housed at the animal facilities of the Institut für Zellbiologie, University of Essen Medical School or at the Institut de recherches cliniques de Montreal, under SPF conditions and according to local animal regulations. Two different strains of Bcl-2 transgenic mice (using the previously described vav-promoter and H2K-promoter [22,28]) were used to ensure that the observed effects were solely due to Bcl-2 over-expression. No difference in phenotype or number of cells was observed between vavBcl-2 tg and H2K-Bcl-2 tg or vav-Gfi1 À/À xBcl-2 tg and Gfi1…”

Section: Gfi1mentioning

confidence: 99%

“…Hence, Gfi1 À/À HSCs are deficient in self-renewal and in their ability to reconstitute hematopoietic lineages in a transplanted host [7,8,10]. Loss of Gfi1 also perturbs early Band T-cell development, the function of mature B-and T-cells and affects myeloid differentiation [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. A particular feature of Gfi1 À/À mice is their increased number of myeloid precursors (CMPs and GMPs) and an increased expression of Hoxa9, a transcription factor involved in AML pathogenesis [1,10,16].…”

Section: Introductionmentioning

confidence: 99%

Growth Factor Independence 1 Protects Hematopoietic Stem Cells Against Apoptosis but Also Prevents the Development of a Myeloproliferative-Like Disease

et al. 2011

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The regulation of gene transcription is elementary for the function of hematopoietic stem cells (HSCs). The transcriptional repressor growth factor independence 1 (Gfi1) restricts HSC proliferation and is essential to maintain their self-renewal capacity and multipotency after transplantation. In addition, Gfi1−/− HSCs are severely compromised in their ability to compete with wild-type (wt) HSCs after transplantation. We now report that Gfi1 protects HSCs against stress-induced apoptosis, probably, by repressing the proapoptotic target gene Bax, since irradiated Gfi1−/− HSCs display higher expression of Bax and show a higher rate of apoptosis than wt HSCs. This protective function of Gfi1 appears to be functionally relevant since Gfi1−/− HSCs that express Bcl-2, which antagonizes the effects of Bax, regain their ability to self renew and to initiate multilineage differentiation after transplantation. Surprisingly, Gfi1−/−xBcl-2 transgenic mice also show a strong, systemic expansion of Mac-1+Gr-1− myeloid cells in bone marrow and peripheral lymphoid organs. These cells express high levels of the proleukemogenic transcription factor Hoxa9 and, in older mice, appear as atypical monocytoid-blastoid cells in the peripheral blood. As a result of this massive expansion of myeloid cells, all Gfi1−/−xBcl-2 mice eventually succumb to a myeloproliferative-like disease resembling a preleukemic state. In summary, our data demonstrate that Gfi1's ability to protect against apoptosis is essential for HSC function. In addition, our finding show that Gfi1 prevents the development of myeloproliferative diseases and provides evidence how Gfi1 deficiency could be linked to myeloid leukemia.

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“…Gfi1 and Gfi1b were found to repress their own transcription and Gfi1b was reported to repress Gfi1 transcription in T cells. [17][18][19] Exogenouslytransduced Gfi1 and Gfi1b proteins may regulate the endogenous expression of Gfi1 and Gfi1b. We then investigated histamine synthesis and tryptase expression in these cells with the transgenes and found no significant changes (Figs.…”

Section: Effect Of Stable Expression Of Gfi1 and Gfi1b In Mc9 Cellsmentioning

confidence: 99%

Regulation of Histamine Synthesis and Tryptase Expression through Transcription Factors, Growth Factor Independent 1 (Gfi1) and Gfi1b, in Murine Cultured Mast Cells

Taura

Furuta

Yamaguchi

et al. 2014

Biological & Pharmaceutical Bulletin

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Mast cells are involved in various immunological responses, although it remains unknown how their terminal differentiation is regulated. We previously established a culture model that mimics the process of mast cell maturation in the cutaneous tissue and found that growth factor independent 1 (Gfi1) was up-regulated whereas its paralogue Gfi1b down-regulated. Here we investigated the roles of Gfi1 and Gfi1b in the process of mast cell maturation using a murine mast cell line, MC9. Gfi1 and Gfi1b cDNAs were stably expressed in MC9 cells using the recombinant lentivirus. Histamine synthesis was significantly induced by stem cell factor (SCF) alone, whereas tryptase expression was significantly augmented in the presence of both SCF and Swiss 3T3 cells. Since exogenously expressed Gfi1 and Gfi1b might affect their expression levels in MC9 cells, we investigated the relationship between the expression profiles of Gfi1/Gfi1b proteins and maturation indices, such as histamine synthesis and tryptase expression. The comparison suggested that histamine synthesis during the co-culture period was positively regulated by Gfi1b while augmented expression of tryptase was abolished by one-sided expression of Gfi1/Gfi1b. Our findings indicated the involvement of Gfi1 and Gfi1b in the process of murine mast cell maturation.Key words mast cell; growth factor independent 1; growth factor independent 1b; histidine decarboxylase; tryptase Mast cells are originated in hematopoietic stem cells in the bone marrow and distributed in nearly all vascularized tissues. Accumulating evidence suggests that mast cells are involved in a wide variety of immunological responses in addition to immediate allergy and protection from parasite infection. 1)When we try to identify the physiological roles of mast cells, it is critical to characterize the nature of local mast cells, because mast cells undergo terminal differentiation in the tissues, in which they are ultimately resident.2) Interleukin-3 (IL-3)-dependent bone marrow-derived cultured mast cells (BMMCs) are one of the most popular murine culture models, although there are many differences between BMMCs and tissue mature mast cells. Levi-Schaffer et al. established a model more similar to mature mast cells distributed in the connective tissues, in which BMMCs were co-cultured with Swiss 3T3 fibroblasts.3) We modified this method to establish a novel culture model, which shares many characteristics with cutaneous mast cells.4) In our model, BMMCs were co-cultured with Swiss 3T3 cells in the presence of stem cell factor (SCF) for 16 d. During this process, cultured mast cells acquired many characteristics of mature cutaneous mast cells, such as potentials of degranulation in response to substance P and compound 48/80, and enhanced expression of granule proteases including chymase, tryptase, and carboxypeptidase A. Since these changes observed during the co-culture period reflected at least in part the process of mast cell maturation, we then investigated the gene expression profiles by microarr...

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Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b

Cited by 71 publications

References 30 publications

Gfi1 and Gfi1b: key regulators of hematopoiesis

Gfi1 and Gfi1b: key regulators of hematopoiesis

Growth Factor Independence 1 Protects Hematopoietic Stem Cells Against Apoptosis but Also Prevents the Development of a Myeloproliferative-Like Disease

Regulation of Histamine Synthesis and Tryptase Expression through Transcription Factors, Growth Factor Independent 1 (Gfi1) and Gfi1b, in Murine Cultured Mast Cells

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