scholarly journals ZNF224 Protein: Multifaceted Functions Based on Its Molecular Partners

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6296
Author(s):  
Elena Cesaro ◽  
Angelo Lupo ◽  
Roberta Rapuano ◽  
Arianna Pastore ◽  
Michela Grosso ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Transcriptional Repression ◽  
Zinc Finger Protein ◽  
Current Knowledge ◽  
Protein Protein Interactions ◽  
Multifunctional Protein ◽  
Finger Protein ◽  
Zinc Finger Domains

The transcription factor ZNF224 is a Kruppel-like zinc finger protein that consists of 707 amino acids and contains 19 tandemly repeated C2H2 zinc finger domains that mediate DNA binding and protein–protein interactions. ZNF224 was originally identified as a transcriptional repressor of genes involved in energy metabolism, and it was demonstrated that ZNF224-mediated transcriptional repression needs the interaction of its KRAB repressor domain with the co-repressor KAP1 and its zinc finger domains 1–3 with the arginine methyltransferase PRMT5. Furthermore, the protein ZNF255 was identified as an alternative isoform of ZNF224 that possesses different domain compositions mediating distinctive functional interactions. Subsequent studies showed that ZNF224 is a multifunctional protein able to exert different transcriptional activities depending on the cell context and the variety of its molecular partners. Indeed, it has been shown that ZNF224 can act as a repressor, an activator and a cofactor for other DNA-binding transcription factors in different human cancers. Here, we provide a brief overview of the current knowledge on the multifaceted interactions of ZNF224 and the resulting different roles of this protein in various cellular contexts.

Insilico Search for Potential DNA Binding Domain of Human Zinc Finger Protein Sp1

2021 ◽  
pp. 217-225
Author(s):  
Sirisha Kaniganti
Keyword(s):  
Dna Binding ◽  
Binding Affinity ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Housekeeping Genes ◽  
Specificity Protein 1 ◽  
Finger Protein ◽  
Zinc Finger Domains ◽  
Specificity Protein ◽  
Regulation Of Growth

Specificity protein 1 (Sp1) belongs to a family of ubiquitously expressed, C2H2-type zinc finger-containing DNA binding proteins that activate or repress transcription of many genes in response to physiological and pathological stimuli. Specificity protein 1 is considered to be a constitutively expressed transcription factor and has been implicated in the regulation of a wide variety of housekeeping genes, tissue-specific genes, and genes involved in the regulation of growth. In order to determine the binding affinity of Sp1 zinc finger domains, the total energy for each and every possible combination of GC box and Zn finger motifs using Hex server, Model IT software’s is calculated. According to the findings of this study, the design of multi-zinc finger proteins with a variety of sequence specificities will be easier to accomplish. Among the three motifs present in Specificity protein 1, motifs 1 and 2 have higher binding affinity than motif 3.

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 Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality.

Genetics ◽  
1992 ◽  
Vol 131 (4) ◽  
pp. 905-916 ◽  
Author(s):  
M Crozatier ◽  
K Kongsuwan ◽  
P Ferrer ◽  
J R Merriam ◽  
J A Lengyel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Essential Gene ◽  
Larval Instar ◽  
Single Amino Acid ◽  
Isolation And Characterization ◽  
Finger Protein

Abstract The Drosophila serendipity (sry) delta (delta) zinc finger protein is a sequence-specific DNA binding protein, maternally inherited by the embryo and present in nuclei of transcriptionally active cells throughout fly development. We report here the isolation and characterization of four ethyl methanesulfate-induced zygotic lethal mutations of different strengths in the sry delta gene. For the stronger allele, all of the lethality occurs during late embryogenesis or the first larval instar. In the cases of the three weaker alleles, most of the lethality occurs during pupation; moreover, those adult escapers that emerge are sterile males lacking partially or completely in spermatozoa bundles. Genetic analysis of sry delta thus indicates that it is an essential gene, whose continued expression throughout the life cycle, notably during embryogenesis and pupal stage, is required for viability. Phenotypic analysis of sry delta hemizygote escaper males further suggests that sry delta may be involved in regulation of two different sets of genes: genes required for viability and genes involved in gonadal development. All four sry delta alleles are fully rescued by a wild-type copy of sry delta, but not by an additional copy of the sry beta gene, reinforcing the view that, although structurally related, these two genes exert distinct functions. Molecular characterization of the four sry delta mutations revealed that these mutations correspond to single amino acid replacements in the sry delta protein. Three of these replacements map to the same (third out of seven) zinc finger in the carboxy-terminal DNA binding domain; interestingly, none affects the zinc finger consensus residues. The fourth mutation is located in the NH2-proximal part of the protein, in a domain proposed to be involved in specific protein-protein interactions.

scholarly journals Overcharging of the Zinc Ion in the Structure of the Zinc-Finger Protein Is Needed for DNA Binding Stability

Biochemistry ◽  
2020 ◽  
Vol 59 (13) ◽  
pp. 1378-1390 ◽  
Author(s):  
Ly H. Nguyen ◽  
Tuyen T. Tran ◽  
Lien Thi Ngoc Truong ◽  
Hanh Hong Mai ◽  
Toan T. Nguyen
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Ion ◽  
Finger Protein

scholarly journals The KAP1 Corepressor Functions To Coordinate the Assembly of De Novo HP1-Demarcated Microenvironments of Heterochromatin Required for KRAB Zinc Finger Protein-Mediated Transcriptional Repression

2006 ◽  
Vol 26 (22) ◽  
pp. 8623-8638 ◽  
Author(s):  
Smitha P. Sripathy ◽  
Jessica Stevens ◽  
David C. Schultz
Keyword(s):  
Rna Polymerase Ii ◽  
Zinc Finger ◽  
Histone Modifications ◽  
Dna Sequences ◽  
Transcriptional Repression ◽  
Zinc Finger Protein ◽  
De Novo ◽  
Regulatory Sequences ◽  
Phd Finger ◽  
Finger Protein

ABSTRACT KAP1/TIF1β is proposed to be a universal corepressor protein for the KRAB zinc finger protein (KRAB-zfp) superfamily of transcriptional repressors. To characterize the role of KAP1 and KAP1-interacting proteins in transcriptional repression, we investigated the regulation of stably integrated reporter transgenes by hormone-responsive KRAB and KAP1 repressor proteins. Here, we demonstrate that depletion of endogenous KAP1 levels by small interfering RNA (siRNA) significantly inhibited KRAB-mediated transcriptional repression of a chromatin template. Similarly, reduction in cellular levels of HP1α/β/γ and SETDB1 by siRNA attenuated KRAB-KAP1 repression. We also found that direct tethering of KAP1 to DNA was sufficient to repress transcription of an integrated transgene. This activity is absolutely dependent upon the interaction of KAP1 with HP1 and on an intact PHD finger and bromodomain of KAP1, suggesting that these domains function cooperatively in transcriptional corepression. The achievement of the repressed state by wild-type KAP1 involves decreased recruitment of RNA polymerase II, reduced levels of histone H3 K9 acetylation and H3K4 methylation, an increase in histone occupancy, enrichment of trimethyl histone H3K9, H3K36, and histone H4K20, and HP1 deposition at proximal regulatory sequences of the transgene. A KAP1 protein containing a mutation of the HP1 binding domain failed to induce any change in the histone modifications associated with DNA sequences of the transgene, implying that HP1-directed nuclear compartmentalization is required for transcriptional repression by the KRAB/KAP1 repression complex. The combination of these data suggests that KAP1 functions to coordinate activities that dynamically regulate changes in histone modifications and deposition of HP1 to establish a de novo microenvironment of heterochromatin, which is required for repression of gene transcription by KRAB-zfps.

scholarly journals Identification, nuclear localization, and DNA-binding activity of the zinc finger protein encoded by the Evi-1 myeloid transforming gene.

1990 ◽  
Vol 10 (3) ◽  
pp. 1259-1264 ◽  
Author(s):  
T Matsugi ◽  
K Morishita ◽  
J N Ihle
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Nuclear Protein ◽  
Zinc Finger Protein ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Double Stranded Dna ◽  
Finger Protein ◽  
Myeloid Leukemias ◽  
Transforming Gene

Activation of the Evi-1 zinc finger gene is a common event associated with transformation of murine myeloid leukemias. To characterize the gene product, we developed antisera against various protein domains. These antisera primarily detected a 145-kilodalton nuclear protein that bound double-stranded DNA. Binding was inhibited by chelating agents and partially restored by zinc ions.

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