scholarly journals Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases

2010 ◽  
Vol 39 (1) ◽  
pp. 381-392 ◽  
Author(s):  
Ankit Gupta ◽  
Xiangdong Meng ◽  
Lihua J. Zhu ◽  
Nathan D. Lawson ◽  
Scot A. Wolfe
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Finger Nucleases ◽  
Finger Protein ◽  
Target Activity

Zinc finger protein 521 antagonizes Runx2 in a deacetylation-dependent manner and increases bone mass in vivo

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S245
Author(s):  
E. Hesse⁎ ◽  
A. Atfi ◽  
R. Kiviranta ◽  
H. Saito ◽  
K. Yamana ◽  
...  
Keyword(s):  
Bone Mass ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Dependent Manner ◽  
Finger Protein

scholarly journals ZNF667 Serves as a Putative Oncogene in Human Hepatocellular Carcinoma

2017 ◽  
Vol 41 (6) ◽  
pp. 2523-2533 ◽  
Author(s):  
Ke Cheng ◽  
Zhizhao Chen ◽  
Lian Liu ◽  
Yujun Zhao ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Bax Protein ◽  
Finger Protein ◽  
Immuno Histochemistry ◽  
Set Up

Background/Aims: Zinc finger protein 667 (ZNF667) is a member of C2H2 zinc finger protein family. For the first time, we aim to analyze the expression pattern of ZNF667 in hepatocellular carcinoma (HCC) tissues; to explore its role in HCC tumorigenesis. Methods: Immuno-histochemistry was carried out to characterize the ZNF667 expression in paraffin-embedded HCC samples. The relationship between ZNF667 expression and the clinical, pathological data of the patients were analyzed. Human normal hepatocyte cells LO2 over expressing ZNF667 (LO2-ZNF667 cells), ZNF667 depleted hepatocellular carcinoma HepG2 cells (HepG2-shZNF667 cells) were set up, their proliferation, migration and invasion abilities were analyzed. Xenograft nude mice were used to analyze the malignancy of HepG2-shZNF667 cells in vivo. Western blot was performed to analyze the expression of Bcl-2 and BAX in LO2-ZNF667 and HepG2-shZNF667 cells. Results: Increased ZNF667 was found via immuno-histochemistry in HCC. Enhanced ZNF667 expression was associated with tumor size, clinical stage and tumor differentiation. LO2-ZNF667 cells displayed increased and HepG2-shZNF667 cells decreased cell proliferation, migration and invasion. Xenograft experiments proved reduced malignancy of HepG2-shZNF667 cells in vivo. LO2-ZNF667 cells displayed increased Bcl-2 and decreased BAX protein expression. HepG2-shZNF667 cells displayed enhanced BAX and inhibited BCL-2 expression. Conclusions: ZNF667 is shown to be a new oncogene in HCC and it may serve as a new therapeutic target for HCC via enhancing BCL-2 and decreasing BAX expression.

TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans

Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3119-3129 ◽  
Author(s):  
P. Chen ◽  
R.E. Ellis
Keyword(s):  
Transcriptional Regulation ◽  
Sexual Identity ◽  
Cell Fate ◽  
Zinc Finger ◽  
Germ Cells ◽  
Zinc Finger Protein ◽  
Rt Pcr ◽  
C Elegans ◽  
Finger Protein

In C. elegans, the zinc-finger protein TRA-1A is thought to be the final arbiter of somatic sexual identity. We show that fog-3, which is required for germ cells to become sperm rather than oocytes, is a target of TRA-1A. First, northern analyses and RT-PCR experiments indicate that expression of fog-3 is controlled by tra-1. Second, studies of double mutants show that this control could be direct. Third, the fog-3 promoter contains multiple sites that bind TRA-1A in gel shift assays, and mutations in these sites alter activity of fog-3 in vivo. These results establish fog-3 as one of the first known targets of transcriptional regulation by TRA-1A. Furthermore, they show that tra-1 controls a terminal regulator of sexual fate in germ cells, just as it is thought to do in the soma.

scholarly journals Correlation between functional and binding activities of designer zinc-finger proteins

2007 ◽  
Vol 403 (1) ◽  
pp. 177-182 ◽  
Author(s):  
Jong Seok Kang
Keyword(s):  
Binding Affinity ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Finger Proteins ◽  
Sequence Specificity ◽  
Binding Assays ◽  
Finger Protein ◽  
Vitro Binding

Rapid progress in the ability to develop and utilize zinc-finger proteins with customized sequence specificity have led to their increasing use as tools for modulation of target gene transcription in the post-genomic era. In the present paper, a series of in vitro binding assays and in vivo reporter analyses were used to demonstrate that a zinc-finger protein can effectively specify a base at each position of the target site in vivo and that functional activity of the zinc-finger protein as either a transcriptional repressor or activator is positively correlated with its binding affinity. In addition, this correlation can be extended to artificial engineered zinc-finger proteins. These data suggest that the binding affinity of designer zinc-finger proteins with novel specificity might be a determinant for their ability to regulate transcription of a gene of interest.

scholarly journals Zinc Finger Protein, Hzf, Is Required for Megakaryocyte Development and Hemostasis

2002 ◽  
Vol 195 (7) ◽  
pp. 941-952 ◽  
Author(s):  
Yuki Kimura ◽  
Adam Hart ◽  
Masanori Hirashima ◽  
Chen Wang ◽  
Doug Holmyard ◽  
...  
Keyword(s):  
Gene Targeting ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Gene Trapping ◽  
Novel Gene ◽  
Finger Protein ◽  
Deficient Mice

Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C2H2-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced α-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of α-granule substances and/or their packing into α-granules during the process of megakaryopoiesis.

scholarly journals ZC3H4—a novel Cys-Cys-Cys-His-type zinc finger protein—is essential for early embryogenesis in mice†

2020 ◽  
Author(s):  
Jianmin Su ◽  
Xiaosu Miao ◽  
Danielle Archambault ◽  
Jesse Mager ◽  
Wei Cui
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Inner Cell Mass ◽  
Functional Characterization ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Cell Number ◽  
Dna Breaks ◽  
Finger Protein

Abstract Zinc finger domains of the Cys-Cys-Cys-His (CCCH) class are evolutionarily conserved proteins that bind nucleic acids and are involved in various biological processes. Nearly 60 CCCH-type zinc finger proteins have been identified in humans and mice, most have not been functionally characterized. Here, we provide the first in vivo functional characterization of ZC3H4—a novel CCCH-type zinc finger protein. Our results show that although Zc3h4 mutant embryos exhibit normal morphology at E3.5 blastocyst stage, they cannot be recovered at E7.5 early post-gastrulation stage, suggesting implantation failure. Outgrowth assays reveal that mutant blastocysts either fail to hatch from the zona pellucida, or can hatch but do not form a typical inner cell mass colony, the source of embryonic stem cells (ESCs). Although there is no change in levels of reactive oxygen species, Zc3h4 mutants display severe DNA breaks and reduced cell proliferation. Analysis of lineage specification reveals that both epiblast and primitive endoderm lineages are compromised with severe reductions in cell number and/or specification in the mutant blastocysts. In summary, these findings demonstrate the essential role of ZC3H4 during early mammalian embryogenesis.

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