GFI1B controls its own expression binding to multiple sites

Anguita, Eduardo; Villegas, Ana; Iborra, Francisco J.; Hernández, Aurora

doi:10.3324/haematol.2009.012351

Cited by 26 publications

(32 citation statements)

References 53 publications

(86 reference statements)

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“…5,15,26,27,[29][30][31] However, it should be noted that examples have been reported in which Gfi1 and Gfi1b can activate gene expression. 15,18,29,32 Gfi1 and Gfi1b also interact physically with other transcription factors through their zinc fingers to co-regulate gene expression (Figures 1 and 2). 17,29,[33][34][35][36] For example, Gfi1 interacts directly with ETS1 to repress the Bax gene through adjacent DNA binding sites.…”

Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

“…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%

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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%

Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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“…We have recently studied Gfi1b regulation through erythropoiesis. As erythroid cells differentiate the general decrease in transcription factor expression, and subsequently of binding to Gfi1b promoter and regulatory elements, correlate with progressive reduction in Gfi1b expression [23]. Nevertheless, in the megakaryocytic lineage, additional unknown factors must be required to achieve Gfi1b repression.…”

Section: Discussionmentioning

confidence: 99%

Human promoter mutations unveil Oct-1 and GATA-1 opposite action on Gfi1b regulation

2010

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Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development. To better understand Gfi1b regulation and to know the implication of the level of expression of this gene in human pathology, we have searched for promoter punctual sequence variations in 214 patients with different hematological diseases. We found two previously unknown congenital mutations at evolutionary conserved GATA and octamer-binding (Oct) transcription factor sites. The Oct site mutation was also found in five relatives of the patient. The GATA motif mutation reduced promoter activity by 50% in vitro, while homozygous patients with the octamer site mutation showed a four-to-five times increase of Gfi1b RNA in platelets. Electrophoretic mobility shift analyses demonstrated that different protein complexes bind to both sites and that binding is reduced by the mutations. Finally, we found that GATA-1 and Oct-1 are the main components of each complex. This study provides evidences of a new mechanism for Gfi1b repression. This is also the first report of Gfi1b mutations with a functional implication; further investigation and follow-up will clarify the involvement of these mutations in hematological disease.

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“…8,15 Gfi1b expression is autoregulated, and it recruits the CoREST complex to its promoter. 8,38 Proteomics analysis demonstrated association of the Hmg20b protein with the CoREST complex in erythroid cells, and we showed direct binding of Hmg20b to the Gfi1b promoter. We, therefore, conclude that Gfi1b-mediated CoREST recruitment to the Gfi1b promoter regulates Gfi1b expression 8,38 ( Figure 6).…”

mentioning

confidence: 99%

“…8,38 Proteomics analysis demonstrated association of the Hmg20b protein with the CoREST complex in erythroid cells, and we showed direct binding of Hmg20b to the Gfi1b promoter. We, therefore, conclude that Gfi1b-mediated CoREST recruitment to the Gfi1b promoter regulates Gfi1b expression 8,38 ( Figure 6). One of the consistently up-regulated genes upon Hmg20b depletion was the Hrasls3 tumor suppressor gene.…”

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The DNA binding factor Hmg20b is a repressor of erythroid differentiation

Esteghamat

Dijk²,

Braun³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established. Design and MethodsTo study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene. ResultsWe show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRASlike suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts. ConclusionsWe conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the downregulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.Key words: Hmg20b, CoREST, erythropoiesis, Gfi1b, Hrasls3, embryonic β-like globins.Citation: Esteghamat F, van Dijk TB, Braun H, Dekker S, van der Linden R, Hou J, Fanis P, Demmers J, van IJcken W, Özgür Z, Horos R, Pourfarzad F, von Lindern M, and

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GFI1B controls its own expression binding to multiple sites

Cited by 26 publications

References 53 publications

Gfi1 and Gfi1b: key regulators of hematopoiesis

Gfi1 and Gfi1b: key regulators of hematopoiesis

Human promoter mutations unveil Oct-1 and GATA-1 opposite action on Gfi1b regulation

The DNA binding factor Hmg20b is a repressor of erythroid differentiation

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