Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

2016 ◽  
Vol 471 (4) ◽  
pp. 533-538
Author(s):  
Yu Ichida ◽  
Yuko Utsunomiya ◽  
Masafumi Onodera
Keyword(s):  
Gene Silencing ◽  
Zinc Finger ◽  
Nuclear Localization ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Finger Protein

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.

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 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.

scholarly journals Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor.

1996 ◽  
Vol 16 (8) ◽  
pp. 4024-4034 ◽  
Author(s):  
P A Zweidler-Mckay ◽  
H L Grimes ◽  
M M Flubacher ◽  
P N Tsichlis
Keyword(s):  
T Cell ◽  
Binding Site ◽  
Electrophoretic Mobility ◽  
Zinc Finger ◽  
Binding Sites ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Mobility Shift ◽  
Finger Protein ◽  
Electrophoretic Mobility Shift Assays

The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2-type, C-terminal zinc finger motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence in culture and in primary retrovirus-induced thymomas. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes. In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in a sequence-specific manner. The Gfi-1 binding site, TAAATCAC(A/T)GCA, was defined via random oligonucleotide selection utilizing a bacterially expressed glutathione S-transferase-Gfi-1 fusion protein. Binding to this site was confirmed by electrophoretic mobility shift assays and DNase I footprinting. Methylation interference analysis and electrophoretic mobility shift assays with mutant oliginucleotides defined the relative importance of specific bases at the consensus binding site. Deletion of individual zinc fingers demonstrated that only zinc fingers 3, 4, and 5 are required for sequence-specific DNA binding. Potential Gfi-1 binding sites were detected in a large number of eukaryotic promoter-enhancers, including the enhancers of several proto-oncogenes and cytokine genes and the enhancer of the human cytomegalovirus (HCMV) major immediate-early promoter, which contains two such sites. HCMV major immediate-early-chloramphenicol acetyltransferase reporter constructs, transfected into NIH 3T3 fibroblasts, were repressed by Gfi-1, and the repression was abrogated by mutation of critical residues in the two Gfi-1 binding sites. These results suggest that Gfi-1 may play a role in HCMV biology and may contribute to oncogenesis and T-cell activation by repressing the expression of genes that inhibit these processes.

scholarly journals Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

1998 ◽  
Vol 12 (4) ◽  
pp. 586-597 ◽  
Author(s):  
W. Gorner ◽  
E. Durchschlag ◽  
M. T. Martinez-Pastor ◽  
F. Estruch ◽  
G. Ammerer ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Zinc Finger ◽  
Nuclear Localization ◽  
Zinc Finger Protein ◽  
C2h2 Zinc Finger ◽  
Finger Protein ◽  
C2h2 Zinc Finger Protein ◽  
Kinase A

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.

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