Transcriptional activation mediated by binding of a plant GATA-type zinc finger protein AGP1 to the AG-motif (AGATCCAA) of the wound-inducibleMybgeneNtMyb2

2003 ◽  
Vol 36 (4) ◽  
pp. 550-564 ◽  
Author(s):  
Kazuhiko Sugimoto ◽  
Shin Takeda ◽  
Hirohiko Hirochika
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Finger Protein

Single zinc-finger extension: enhancing transcriptional activity and specificity of three-zinc-finger proteins

2005 ◽  
Vol 386 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Alexander E.F. Smith ◽  
Farzin Farzaneh ◽  
Kevin G. Ford
Keyword(s):  
Transcription Factors ◽  
Fusion Protein ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Zinc Finger Proteins ◽  
Finger Protein ◽  
Finger Extension ◽  
Vp16 Fusion

AbstractIn order to demonstrate that an existing zinc-finger protein can be simply modified to enhance DNA binding and sequence discrimination in both episomal and chromatin contexts using existing zinc-finger DNA recognition code data, and without recourse to phage display and selection strategies, we have examined the consequences of a single zinc-finger extension to a synthetic three-zinc-finger VP16 fusion protein, on transcriptional activation from model target promoters harbouring the zinc-finger binding sequences. We report a nearly 10-fold enhanced transcriptional activation by the four-zinc-finger VP16 fusion protein relative to the progenitor three-finger VP16 protein in transient assays and a greater than five-fold enhancement in stable reporter-gene expression assays. A marked decrease in transcriptional activation was evident for the four-zinc-finger derivative from mutated regulatory regions compared to the progenitor protein, as a result of recognition site-size extension. This discriminatory effect was shown to be protein concentration-dependent. These observations suggest that four-zinc-finger proteins are stable functional motifs that can be a significant improvement over the progenitor three-zinc-finger protein, both in terms of specificity and the ability to target transcriptional function to promoters, and that single zinc-finger extension can therefore have a significant impact on DNA zinc-finger protein interactions. This is a simple route for modifying or enhancing the binding properties of existing synthetic zinc-finger-based transcription factors and may be particularly suited for the modification of endogenous zinc-finger transcription factors for promoter biasing applications.

scholarly journals Broadly active zinc finger protein-guided transcriptional activation of HIV-1

2021 ◽  
Vol 20 ◽  
pp. 18-29
Author(s):  
Tristan A. Scott ◽  
Denis O’Meally ◽  
Nicole Anne Grepo ◽  
Citradewi Soemardy ◽  
Daniel C. Lazar ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Hiv 1

scholarly journals Transcriptional activation ofBrassica napusβ-ketoacyl-ACP synthase II with an engineered zinc finger protein transcription factor

2012 ◽  
Vol 10 (7) ◽  
pp. 783-791 ◽  
Author(s):  
Manju Gupta ◽  
Russell C. DeKelver ◽  
Asha Palta ◽  
Carla Clifford ◽  
Sunita Gopalan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Protein Transcription

scholarly journals Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li-Xin Ren ◽  
Jin-Chun Qi ◽  
An-Ning Zhao ◽  
Bei Shi ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Clear Cell ◽  
Kidney Tissue ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Finger Protein ◽  
The Relationship

Abstract Background The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. Methods MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. Results MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. Conclusion These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

scholarly journals Zinc Finger Protein Gfi1 Controls the Endotoxin-Mediated Toll-Like Receptor Inflammatory Response by Antagonizing NF-κB p65

2010 ◽  
Vol 30 (16) ◽  
pp. 3929-3942 ◽  
Author(s):  
Ehssan Sharif-Askari ◽  
Lothar Vassen ◽  
Christian Kosan ◽  
Cyrus Khandanpour ◽  
Marie-Claude Gaudreau ◽  
...  
Keyword(s):  
Septic Shock ◽  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Nuclear Translocation ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Finger Protein ◽  
Tnf Α

ABSTRACT Endotoxin (bacterial lipopolysaccharide [LPS]) causes fatal septic shock via the Toll-like receptor 4 (TLR-4) protein present on innate immunity effector cells, which activates nuclear factor kappa B (NF-κB), inducing proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α). An early step in this process involves nuclear sequestration of the p65-RelA NF-κB subunit, enabling transcriptional activation of target inflammatory cytokine genes. Here, we analyzed the role of the nuclear zinc finger protein Gfi1 in the TLR response using primary bone marrow-derived macrophages. We show that upon LPS stimulation, expression of Gfi1 is induced with kinetics similar to those of nuclear translocation of p65 and that Gfi1 interacts with p65 and inhibits p65-mediated transcriptional transactivation by interfering with p65 binding to target gene promoter DNA. Gfi1-deficient macrophages show abnormally high mRNA levels of the TNF-α gene and many other p65 target genes and a higher rate of TNF promoter occupancy by p65 than wild-type cells after LPS stimulation, suggesting that Gfi1 functions as an antagonist of NF-κB activity at the level of promoter binding. Our findings identify a new function of Gfi1 as a general negative regulator of the endotoxin-initiated innate immune responses, including septic shock and possibly other severe inflammatory diseases.

scholarly journals Broadly active zinc finger protein-guided transcriptional activation of HIV

2020 ◽  
Author(s):  
tristan Scott ◽  
Denis V O'Meally ◽  
Nicole Anne Grepo ◽  
Citradewi Soemardy ◽  
Daniel lazar ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Gene Activation ◽  
Host Cells ◽  
Finger Protein ◽  
Substantial Progress ◽  
Shock And Kill ◽  
Latent Hiv ◽  
Hiv 1

Abstract Background Human Immunodeficiency Virus type 1 (HIV-1) is a lentivirus that causes a persistent viral infection and results in the demise of immune regulatory cells. Clearance of HIV-1 infection by the immune system is inefficient, and integration of proviral DNA into the genome of host cells provides a means for evasion and long-term persistence. A therapeutic compound that specifically targets and sustainably activates a latent HIV provirus could be transformative and is an overarching goal for the “shock-and-kill” approach to a functional cure for HIV. Results Substantial progress has been made towards the development of recombinant proteins that can target specific genomic loci for gene activation, repression or inactivation by directed mutations. However, most of these modalities are too large, or too complex, for efficient therapeutic application. We describe here the development and testing of a novel recombinant zinc finger protein transactivator, ZFPb-362-VPR, which specifically and potently enhances proviral HIV transcription both in established latency models and across different viral clades. Additionally, ZFP-362-VPR activated HIV reporter gene expression in a well-established primary human CD4+ T-cell latency model and was specific in targeting the HIV LTR as determined from off-target transcriptome analyses. Conclusions: This study provides clear proof of concept for the application of a novel, and therapeutically relevant, protein transactivator to purge cellular reservoirs of HIV-1.

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