IgM receptor-mediated transactivation of the IgH 3′ enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.

Grant, Patrick A.; Thompson, Craig B.; Pettersson, Sven

doi:10.1002/j.1460-2075.1995.tb00129.x

Cited by 65 publications

(47 citation statements)

References 61 publications

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“…Considering the body of evidence that suggests that Ets/AP-1 cooperate for full transcriptional activation, it seems likely that this may be the function of the Ϫ76/Ϫ58 element. For instance similar cooperation between Ets and AP-1 occurs through a juxtaposed Ets/AP-1-binding site in the polyoma virus enhancer (18) and has subsequently been implicated in the regulation of genes involved in invasion and metastasis, including collagenase and urokinase plasminogen activator (19,(33)(34)(35)(36)(37). Although we found that the collagenase Ets element or the polyoma virus Ets element did not effectively compete for binding to the FGF-BP Ets element, this may reflect the binding of another Ets family member to the FGF-BP promoter whose recognition site could be determined by sequences flanking the GGA core (27).…”

Section: Discussionmentioning

confidence: 99%

Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements

Harris¹,

Liaudet-Coopman²,

Boyle

et al. 1998

Journal of Biological Chemistry

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Earlier studies from our laboratory showed that a secreted binding protein for fibroblast growth factors (FGF-BP) is expressed at high levels in squamous cell carcinoma (SCC) cell lines. Overexpression studies or conversely reduced expression of FGF-BP by ribozyme targeting have elucidated a direct role of this protein in angiogenesis during tumor development. We have also observed a significant up-regulation of FGF-BP during TPA (12-O-tetradecanoylphorbol-13-acetate) promotion of skin cancer. Here we investigate the mechanism of TPA induction of FGF-BP gene expression in the human ME-180 SCC cell line. We found that TPA increased FGF-BP mRNA levels in a time-and dose-dependent manner mediated via the protein kinase C signal transduction pathway. Results from actinomycin D and cycloheximide experiments as well as nuclear transcription assays revealed that TPA up-regulated the steadystate levels of FGF-BP mRNA by increasing its rate of gene transcription independently of de novo protein synthesis. We isolated the human FGF-BP promoter and determined by deletion analysis that TPA regulatory elements were all contained in the first 118 base pairs upstream of the transcription start site. Further mutational analysis revealed that full TPA induction required interplay between several regulatory elements with homology to Ets, AP-1, and CAATT/enhancer binding protein C/EBP sites. In addition, deletion or mutation of a 10-base pair region juxtaposed to the AP-1 site dramatically increased TPA induced FGF-BP gene expression. This region represses the extent of the FGF-BP promoter response to TPA and contained sequences recognized by the family of E box helix-loop-helix transcription factors. Gel shift analysis showed specific and TPA-inducible protein binding to the Ets, AP-1, and C/EBP sites. Furthermore, distinct, specific, and TPAinducible binding to the imperfect E box repressor element was also apparent. Overall, our data indicate that TPA effects on FGF-BP gene transcription are tightly controlled by a complex interplay of positive elements and a novel negative regulatory element.

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Section: Discussionmentioning

confidence: 99%

Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements

Harris¹,

Liaudet-Coopman²,

Boyle

et al. 1998

Journal of Biological Chemistry

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“…Since this initial description, the transcriptional activation of other genes has also been shown to require RREs. Rasstimulated RRE promoter elements are able to activate the expression of genes known to be involved in cellular transformation and migration, including uPA, stromelysin-1 (MMP-3) and collagenase-1 (MMP-1) (Aoyama and Klemenz, 1993;Bortner et al, 1993;Chambers and Tuck, 1993;Grant et al, 1995;Wasylyk et al, 1991;Wu et al, 1994). Ras-responsiveness can be blocked by dominant-negative members of the AP1 and Ets families (Bortner et al, 1993;Galang et al, 1994;Gutman and Wasylyk, 1991;Langer et al, 1992;Lloyd et al, 1991;Wasylyk et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Signal transduction and the Ets family of transcription factors

2000

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“…The factors Ets-1, Elf-1, and PU.1 bind to various sites within the IgH intronic enhancer (10 -12). The 3Ј regulatory region contains binding sites for both Elf-1 and PU.1 (13,14). The Ets transcription factor PU.1 is predicted to be important in B cell development based on two observations.…”

mentioning

confidence: 99%

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

Schweitzer

Huang

Kamath

et al. 2006

The Journal of Immunology

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The Ets transcription factor Spi-C, expressed in B cells and macrophages, is closely related to PU.1 and has the ability to recognize the same DNA consensus sequence. However, the function of Spi-C has yet to be determined. The purpose of this study is to further examine Spi-C activity in B cell development. First, using retroviral vectors to infect PU.1−/− fetal liver progenitors, Spi-C was found to be inefficient at inducing cytokine-dependent proliferation and differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7-dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi-C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro-B cells express increased levels of IgH sterile transcripts and reduced levels of expression and transcription of the FcγRIIb gene. Gel-shift analysis suggests that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites in the IgH intronic enhancer and FcγRIIb promoter. Transient transfection analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer and activate the FcγRIIb promoter, while Spi-C opposes these activities. WT-Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3 within the IgH 3′ regulatory region, indicating that Spi-C can contribute to removal of repressive features in the IgH locus. Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes.

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IgM receptor-mediated transactivation of the IgH 3′ enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.

Abstract: The function of the temporally regulated B lymphocytespecific immunoglobulin heavy chain (IgH) 3

Cited by 65 publications

References 61 publications

Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements

Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements

Signal transduction and the Ets family of transcription factors

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

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