scholarly journals Drosophila Zinc Finger Protein CG9890 Is Colocalized with Chromatin Modifying and Remodeling Complexes on Gene Promoters and Involved in Transcription Regulation

Acta Naturae ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 114-119
Author(s):  
N. A. Fursova ◽  
M. Y. Mazina ◽  
J. V. Nikolenko ◽  
N. E. Vorobyova ◽  
A. N. Krasnov
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Promoters ◽  
Replication Complex ◽  
Finger Protein ◽  
Genome Wide ◽  
A Genome ◽  
Nucleosome Density ◽  
Genome Wide Study ◽  
Transcription And Replication

In this work, we conducted a genome-wide study of the zinc finger protein CG9890 and showed that it is localized mostly on the promoters of active genes. The CG9890 binding sites are low-nucleosome-density regions and are colocalized with the chromatin modifying and remodeling complexes SAGA and dSWI/SNF, as well as with the ORC replication complex. The CG9890 protein was shown to be involved in the regulation of the expression of some genes on the promoters of which it is located, with the ecdysone cascade genes accounting for a significant percentage of these genes. Thus, the CG9890 protein is a new member of the transcriptional network which is localized on active promoters, interacts with the main transcription and replication complexes, and is involved in the regulation of both basal and inducible transcription.

scholarly journals AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne Schuster ◽  
Eliane Klein ◽  
Virginie Neirinckx ◽  
Arnon Møldrup Knudsen ◽  
Carina Fabian ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Primary Brain Tumor ◽  
Cellular Models ◽  
Finger Protein ◽  
Genome Wide ◽  
A Genome ◽  
Complete Surgical Resection ◽  
Invasive Capacity ◽  
Activate Gene

AbstractThe infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted.

scholarly journals Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

2020 ◽  
Vol 21 (16) ◽  
pp. 5762
Author(s):  
Andrea Balogh ◽  
Lilla Reiniger ◽  
Szabolcs Hetey ◽  
Peter Kiraly ◽  
Eszter Toth ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Malignant Tumors ◽  
Trophoblast Invasion ◽  
Normal Brain ◽  
Protein Levels ◽  
Finger Protein ◽  
Genome Wide ◽  
Transcriptomic Changes ◽  
The Brain

Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein subfamily, is predominantly expressed in the brain and placenta in humans. Recently, we unveiled that ZNF554 regulates trophoblast invasion during placentation and its decreased expression leads to the early pathogenesis of preeclampsia. Since ZNF proteins are immensely implicated in the development of several tumors including malignant tumors of the brain, here we explored the pathological role of ZNF554 in gliomas. We examined the expression of ZNF554 at mRNA and protein levels in normal brain and gliomas, and then we searched for genome-wide transcriptomic changes in U87 glioblastoma cells transiently overexpressing ZNF554. Immunohistochemistry of brain tissues in our cohort (n = 62) and analysis of large TCGA RNA-Seq data (n = 687) of control, oligodendroglioma, and astrocytoma tissues both revealed decreased expression of ZNF554 towards higher glioma grades. Furthermore, low ZNF554 expression was associated with shorter survival of grade III and IV astrocytoma patients. Overexpression of ZNF554 in U87 cells resulted in differential expression, mostly downregulation of 899 genes. The “PI3K-Akt signaling pathway”, known to be activated during glioma development, was the most impacted among 116 dysregulated pathways. Most affected pathways were cancer-related and/or immune-related. Congruently, cell proliferation was decreased and cell cycle was arrested in ZNF554-transfected glioma cells. These data collectively suggest that ZNF554 is a potential tumor suppressor and its decreased expression may lead to the loss of oncogene suppression, activation of tumor pathways, and shorter survival of patients with malignant glioma.

scholarly journals Genome-wide Regulatory Roles of the C2H2-type Zinc Finger Protein ZNF764 on the Glucocorticoid Receptor

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer Fadda ◽  
Najeeb Syed ◽  
Rafah Mackeh ◽  
Anna Papadopoulou ◽  
Shigeru Suzuki ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Genome Wide

scholarly journals The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of the Drosophila male X-chromosome

2020 ◽  
Author(s):  
William Jordan ◽  
Erica Larschan
Keyword(s):  
Long Range ◽  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Zinc Finger Protein ◽  
Dimensional Space ◽  
Active Chromatin ◽  
Single Male ◽  
Finger Protein ◽  
Genome Wide

SummaryDrosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The Male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that on the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Here, we demonstrate that CLAMP promotes the observed clustering of MSLc bindings sites. Genome-wide, CLAMP promotes interactions between active chromatin regions. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes interactions between active chromatin regions together with other insulator proteins. Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

2018 ◽  
Vol 96 (10) ◽  
pp. 971-976 ◽  
Author(s):  
Anwesha Laha ◽  
Avisek Majumder ◽  
Mahavir Singh ◽  
Suresh C. Tyagi
Keyword(s):  
Zinc Finger ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Zinc Finger Protein ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Divalent Metal Ions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Finger Protein

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu2+ and Zn2+, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

scholarly journals Yeast PalA/AIP1/Alix Homolog Rim20p Associates with a PEST-Like Region and Is Required for Its Proteolytic Cleavage

2001 ◽  
Vol 183 (23) ◽  
pp. 6917-6923 ◽  
Author(s):  
Wenjie Xu ◽  
Aaron P. Mitchell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Zinc Finger ◽  
Cysteine Protease ◽  
Zinc Finger Protein ◽  
Mutant Proteins ◽  
Finger Protein ◽  
Genome Wide ◽  
Close Proximity ◽  
Two Hybrid

ABSTRACT The Saccharomyces cerevisiae zinc finger protein Rim101p is activated by cleavage of its C-terminal region, which resembles PEST regions that confer susceptibility to proteolysis. Here we report that Rim20p, a member of the broadly conserved PalA/AIP1/Alix family, is required for Rim101p cleavage. Two-hybrid and coimmunoprecipitation assays indicate that Rim20p binds to Rim101p, and a two-hybrid assay shows that the Rim101p PEST-like region is sufficient for Rim20p binding. Rim101p-Rim20p interaction is conserved in Candida albicans, supporting the idea that interaction is functionally significant. Analysis of Rim20p mutant proteins indicates that some of its broadly conserved regions are required for processing of Rim101p and for stability of Rim20p itself but are not required for interaction with Rim101p. A recent genome-wide two-hybrid study (T. Ito, T. Chiba, R. Ozawa, M. Yoshida, M. Hattori, and Y. Sakaki, Proc. Natl. Acad. Sci. USA 98:4569–4574, 2000) indicates that Rim20p interacts with Snf7p and that Snf7p interacts with Rim13p, a cysteine protease required for Rim101p proteolysis. We suggest that Rim20p may serve as part of a scaffold that places Rim101p and Rim13p in close proximity.

scholarly journals Transcriptional Regulation of the CLC-K1 Promoter by myc-Associated Zinc Finger Protein and Kidney-Enriched Krüppel-Like Factor, a Novel Zinc Finger Repressor

2000 ◽  
Vol 20 (19) ◽  
pp. 7319-7331 ◽  
Author(s):  
Shinichi Uchida ◽  
Yujiro Tanaka ◽  
Hiroshi Ito ◽  
Fumiko Saitoh-Ohara ◽  
Johji Inazawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Mesangial Cells ◽  
Specific Binding ◽  
Consensus Sequence ◽  
Interstitial Cells ◽  
Luciferase Reporter ◽  
Gene Promoters ◽  
Finger Protein

ABSTRACT The expression of CLC-K1 and CLC-K2, two kidney-specific CLC chloride channels, is transcriptionally regulated on a tissue-specific basis. Previous studies have shown that a GA element near their transcriptional start sites is important for basal and cell-specific activities of the CLC-K1 and CLC-K2 gene promoters. To identify the GA-binding proteins, the human kidney cDNA library was screened by a yeast one-hybrid system. A novel member of the Cys2-His2 zinc finger gene designated KKLF (for “kidney-enriched Krüppel-like factor”) and the previously isolated MAZ (for “myc-associated zinc finger protein”) were cloned. KKLF was found to be abundantly expressed in the liver, kidneys, heart, and skeletal muscle, and immunohistochemistry revealed the nuclear localization of KKLF protein in interstitial cells in heart and skeletal muscle, stellate cells, and fibroblasts in the liver. In the kidneys, KKLF protein was localized in interstitial cells, mesangial cells, and nephron segments, where CLC-K1 and CLC-K2 were not expressed. A gel mobility shift assay revealed sequence-specific binding of recombinant KKLF and MAZ proteins to the CLC-K1 GA element, and the fine-mutation assay clarified that the consensus sequence for the KKLF binding site was GGGGNGGNG. In a transient-transfection experiment, MAZ had a strong activating effect on transcription of the CLC-K1–luciferase reporter gene. On the other hand, KKLF coexpression with MAZ appeared to block the activating effect of MAZ. These results suggest that a novel set of zinc finger proteins may help regulate the strict tissue- and nephron segment-specific expression of the CLC-K1 and CLC-K2 channel genes through their GA cis element.

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