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 Characterization of a Novel Gene Encoding a Putative Single Zinc-finger Protein,ZIM, Expressed during the Reproductive Phase inArabidopsis thaliana

2000 ◽  
Vol 64 (7) ◽  
pp. 1402-1409 ◽  
Author(s):  
Akiko NISHII ◽  
Miho TAKEMURA ◽  
Hidetomo FUJITA ◽  
Masahito SHIKATA ◽  
Akiho YOKOTA ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Encoding ◽  
Novel Gene ◽  
Finger Protein ◽  
Reproductive Phase

The Regulation of Zinc Finger Proteins by Mirnas Enriched in ALL-Microvesicles

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1448-1448
Author(s):  
Huiyu Li ◽  
Xiaomei Chen ◽  
Wei Xiong ◽  
Fang Liu ◽  
Shiang Huang
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Expression Profiles ◽  
Zinc Fingers ◽  
Zinc Finger Proteins ◽  
Bioactive Molecules ◽  
Chromosomal Protein ◽  
Normal Peripheral Blood ◽  
Finger Protein

Abstract Abstract 1448 Microvesicles (MVs) are submicrometric membrane fragments and they can “hijack” membrane components and engulf cytoplasmic contents from their cellular origin. MVs are enriched in various bioactive molecules of their parental cells, such as proteins, DNA, mRNA and miRNAs. Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA (miRNA) between cells. MVs miRNAs may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. We determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. We identified 182 and 166 dysregulated miRNAs in MVs derived from Nalm 6 cells and from Jurkat cells, respectively. Both up regulated (123/182 in Nalm 6-MVs and 114/166 in Jurkat- MVs) and down regulated (59/182 in Nalm 6-MVs and 52/166 in Jurkat- MVs) expressions were observed compared with MVs from normal peripheral blood the MVs normal control. When we analyzed those miRNA with bioinformatic tools (TargetScan), we found an interesting phenomenon that presence of 111 zinc fingers genes were regulated by 52 miRNAs, indicating that the ALL-microvesicles were enriched with miRNAs regulating zinc finger proteins. They encompassed zinc fingers and homeoboxes 2, zinc finger, ZZ-type containing 3, zinc finger, SWIM-type containing 1, zinc finger, RAN-binding domain containing 3, zinc finger, NFX1-type containing 1, zinc finger, MYM-type 4, zinc finger, FYVE domain containing 1 and their 5 subtypes; zinc finger, DHHC-type containing16, and other subtypes; zinc finger, CCHC domain containing 14 and 7A, zinc finger, BED-type containing 4; zinc finger protein, X-linked; zinc finger protein, multitype 2; zinc finger protein 81, and their 55 subtypes; zinc finger and SCAN domain containing 18, zinc finger and BTB domain containing 9. ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. This provides clues that genes commonly function together. It is worth noting that 52 miRNA regulating above zinc finger protein genes were up-expressed, suggeting that miRNA regulating zinc fingers were active in ALL-MVs. Zinc finger proteins are important transcriptions in eukaryotes and play roles in regulating gene. Some members of the Zinc finger family have close relationaship with tumour. Zinc finger X-chromosomal protein (Zfx) is a protein that in humans is encoded by the ZFX gene. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, gastric tumoural tissues, and leukemia. [1,2]. Zinc finger and homeoboxes 2 (ZHX2) was target gene of miRNA-1260. The role of miRNA are negatively regulated host gene expressions. ZHX2 inhibits HCC cell proliferation by preventing expression of Cyclins A and E, and reduces growth of xenograft tumors. Loss of nuclear ZHX2 might be an early step in the development of HCC[3]. In our study, the miRNA-1260 were 9 fold higher in ALL MVs. In leukeima microenvironment, ALL-MVs may transfer aberantly expressed miRNAs to their target cell lead to abnormally regulated the zinc finger proteins that may play roles in ALL. In this study, we demonstrated that ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. Futhermore, Zinc fingers were active in ALL-MVs and commonly function together. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Why Do Long Zinc Finger Proteins have Short Motifs?

2019 ◽  
Author(s):  
Zheng Zuo ◽  
Timothy Billings ◽  
Michael Walker ◽  
Petko Petkov ◽  
Polly Fordyce ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Motif Discovery ◽  
Prediction Models ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Zinc Finger Proteins ◽  
General Mechanism ◽  
Core Motif

SummaryThe human genome has more than 800 C2H2 Zinc Finger-containing genes, and many of them are composed of long tandem arrays of zinc fingers. Current Zinc Finger Protein (ZFP) motif prediction models assume longer finger arrays correspond to longer DNA-binding motifs and higher specificity. However, recent experimental efforts to identify ZFP binding sites in vivo contradict this assumption with many having short reported motifs. Using Zinc Finger Y (ZFY), which has 13 ZFs, we quantitatively characterize its DNA binding specificity with several complementary methods, including Affinity-seq, HT-SELEX, Spec-seq and fluorescence anisotropy. Besides the previously identified core motif GGCCT recognized by fingers 12-13, we find a novel secondary irregular motif recognized by accessory fingers. Via high-throughput energy measurements and two-color anisotropy, we establish that this secondary motif contributes to binding and recognition in a non-independent manner, increasing overall affinity only in the presence of the core recognition site. Through additional experimental and iterative computational analysis of CTCF and ZNF343, we further establish that this non-independent recognition between core and secondary motifs could be a general mechanism for tandem zinc finger proteins. These results establish that better motif discovery methods that consider the intrinsic properties of tandem zinc fingers including irregular motif structure, variable spacing and non-independent recognition are essential to improve prediction of ZFP recognition, occupancies, and effects on downstream gene expression in vivo.

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

Evi3, a common retroviral integration site in murine B-cell lymphoma, encodes an EBFAZ-related Krüppel-like zinc finger protein

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1934-1940 ◽  
Author(s):  
Søren Warming ◽  
Pentao Liu ◽  
Takeshi Suzuki ◽  
Keiko Akagi ◽  
Susan Lindtner ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Integration Site ◽  
Zinc Fingers ◽  
B Cell Lymphoma ◽  
Retroviral Integration ◽  
Finger Protein ◽  
Early B Cell Factor

Retroviral insertional mutagenesis in inbred mouse strains provides a powerful method for cancer gene discovery. Here, we show that a common retroviral integration site (RIS) in AKXD B-cell lymphomas, termed Evi3, encodes a novel zinc finger protein with 30 Krüppel-like zinc finger repeats. Most integrations atEvi3 are located upstream of the first translated exon and result in 3′ long-terminal repeat (LTR)–driven overexpression ofEvi3. Evi3 is highly related to the early B-cell factor–associated zinc finger gene (Ebfaz), and all 30 zinc fingers found in EVI3 are conserved in EBFAZ. EBFAZ binds to and negatively regulates early B-cell factor (EBF) (also known as olfactory-1, OLF1), a basic helix-loop-helix (bHLH) transcription factor required for B-lineage commitment and the development of the olfactory epithelium. EBFAZ also binds to SMA- and MAD-related protein–1 (SMAD1) and SMAD4 in response to bone morphogenetic protein–2 (BMP2) signaling, which in turn activates the homeobox regulator of Xenopus mesoderm and neural development Xvent-2. Surprisingly, while Ebfazand Evi3 are coexpressed in many tissues, and both proteins are nuclear, we could not detect Ebfaz expression in B cells by reverse transcriptase–polymerase chain reaction (RT-PCR), whereas Evi3 expression could be detected at all stages of B-cell development. Our results suggest that EVI3, like EBFAZ, is a multifunctional protein that participates in many signaling pathways via its multiple zinc fingers. Furthermore, our results suggest that EVI3, not EBFAZ, is the member of this protein family that interacts with and regulates EBF in B cells.

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.

scholarly journals Transcriptional Activities of the Zinc Finger Protein Zac Are Differentially Controlled by DNA Binding

2003 ◽  
Vol 23 (3) ◽  
pp. 988-1003 ◽  
Author(s):  
Anke Hoffmann ◽  
Elisabetta Ciani ◽  
Joel Boeckardt ◽  
Florian Holsboer ◽  
Laurent Journot ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Repeat Elements ◽  
Functional Connections ◽  
Finger Protein ◽  
Dna Binding Sites ◽  
Transcriptional Regulatory ◽  
Dna Elements

ABSTRACT Zac encodes a zinc finger protein that promotes apoptosis and cell cycle arrest and is maternally imprinted. Here, we show that Zac contains transactivation and repressor activities and that these transcriptional activities are differentially controlled by DNA binding. Zac transactivation mapped to two distinct domains. One of these contained multiple repeats of the peptide PLE, which behaved as an autonomous activation unit. More importantly, we identified two related high-affinity DNA-binding sites which were differentially bound by seven Zac C2H2 zinc fingers. Zac bound as a monomer through zinc fingers 6 and 7 to the palindromic DNA element to confer transactivation. In contrast, binding as a monomer to one half-site of the repeat element turned Zac into a repressor. Conversely, Zac dimerization at properly spaced direct and reverse repeat elements enabled transactivation, which strictly correlated with DNA-dependent and -independent contacts of key residues within the recognition helix of zinc finger 7. The later ones support specific functional connections between Zac DNA binding and transcriptional-regulatory surfaces. Both classes of DNA elements were identified in a new Zac target gene and confirmed that the zinc fingers communicate with the transactivation function. Together, our data demonstrate a role for Zac as a transcription factor in addition to its role as coactivator for nuclear receptors and p53.

scholarly journals Two types of zinc fingers are required for dimerization of the serendipity delta transcriptional activator.

1997 ◽  
Vol 17 (6) ◽  
pp. 3137-3145 ◽  
Author(s):  
F Payre ◽  
P Buono ◽  
N Vanzo ◽  
A Vincent
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Point Mutations ◽  
Transcriptional Activator ◽  
Consensus Binding Site ◽  
Finger Protein ◽  
Synergistic Activation ◽  
Dna Binding Affinity

The serendipity (sry) delta zinc finger protein controls bicoid gene expression during Drosophila melanogaster oogenesis. In addition, sry delta mutants display various zygotic phenotypes, ranging from abnormal embryogenesis to sex-biased adult lethality. We report here that sry delta is a sequence-specific transcriptional activator. A single sry delta consensus binding site (SDCS), in either orientation, is sufficient to promote transcription activation in cell culture, and multiple SDCSs mediate a strong synergistic activation, reflecting the cooperativity of sry delta binding to DNA. Further, several lines of evidence strongly suggest that sry delta binds to DNA as a dimer. While each of three point mutations located in the third zinc finger of sry delta drastically reduces its DNA binding affinity, a fourth mutation, located in the N-terminal region of the protein, specifically affects the cooperativity of DNA binding. This mutation reveals the functional importance of a putative Cys2/Cys2 zinc finger motif of a novel type, located outside the DNA binding domain. A systematic deletion analysis shows that interaction between this proposed Cys2/Cys2 motif and a classical Cys2/His2 zinc finger mediates homodimerization, which is required for DNA binding cooperativity.

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