scholarly journals trans Repression of the Human Metallothionein IIA Gene Promoter by PZ120, a Novel 120-Kilodalton Zinc Finger Protein

1999 ◽  
Vol 19 (1) ◽  
pp. 680-689 ◽  
Author(s):  
Chih-Min Tang ◽  
Jennifer Westling ◽  
Edward Seto
Keyword(s):  
Zinc Finger ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Zinc Finger Protein ◽  
Gene Promoter ◽  
Initiation Site ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Finger Protein ◽  
Eukaryotic Organisms

ABSTRACT Metallothioneins are small, highly conserved, cysteine-rich proteins that bind a variety of metal ions. They are found in virtually all eukaryotic organisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as binding sites fortrans-acting factors such as Sp1, AP1, AP2, AP4, and the glucocorticoid receptor, the hMTIIA promoter contains eight consensus metal response element sequences. We report here the cloning of a novel zinc finger protein with a molecular mass of 120 kDa (PZ120) that interacts specifically with the hMTIIA transcription initiation site. The PZ120 protein is ubiquitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcription factors. Intriguingly, we found that a region of PZ120 outside of the zinc finger domain can bind specifically to the hMTIIA DNA. Using transient-transfection analysis, we found that PZ120 repressed transcription of the hMTIIA promoter. These results suggest that the hMTIIA gene is regulated by an additional negative regulator that has not been previously described.

Zinc-finger protein MdBBX7/MdCOL9, a target of MdMIEL1 E3 ligase, confers drought tolerance in apple

2021 ◽  
Author(s):  
Pengxiang Chen ◽  
Fang Zhi ◽  
Xuewei Li ◽  
Wenyun Shen ◽  
Mingjia Yan ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
E3 Ligase ◽  
26S Proteasome ◽  
Negative Regulator ◽  
Binding Motif ◽  
Ethylene Response Factor ◽  
Finger Protein

Abstract Water deficit is one of the main challenges for apple (Malus × domestica) growth and productivity. Breeding drought-tolerant cultivars depends on a thorough understanding of the drought responses of apple trees. Here, we identified the zinc-finger protein B-BOX 7/CONSTANS-LIKE 9 (MdBBX7/MdCOL9), which plays a positive role in apple drought tolerance. The overexpression of MdBBX7 enhanced drought tolerance, whereas knocking down MdBBX7 expression reduced it. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis identified one cis-element of MdBBX7, CCTTG, as well as its known binding motif, the T/G box. ChIP-seq and RNA-seq identified 1,197 direct targets of MdBBX7, including ETHYLENE RESPONSE FACTOR (ERF1), EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15), and GOLDEN2-LIKE 1 (GLK1) and these were further verified by ChIP-qPCR and electronic mobility shift assays. Yeast two-hybrid screen identified an interacting protein of MdBBX7, RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1). Further examination revealed that MdMIEL1 could mediate the ubiquitination and degradation of MdBBX7 by the 26S proteasome pathway. Genetic interaction analysis suggested that MdMIEL1 acts as an upstream factor of MdBBX7. In addition, MdMIEL1 was a negative regulator of the apple drought stress response. Taken together, our results illustrate the molecular mechanisms by which the MdMIEL1–MdBBX7 module influences the response of apple to drought stress.

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 Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso

2012 ◽  
Vol 109 (38) ◽  
pp. 15229-15234 ◽  
Author(s):  
Bethany A. Buck-Koehntop ◽  
Robyn L. Stanfield ◽  
Damian C. Ekiert ◽  
Maria A. Martinez-Yamout ◽  
H. Jane Dyson ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Zinc Finger ◽  
Dna Sequences ◽  
Genome Stability ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Epigenetic Modification ◽  
Cpg Dinucleotides ◽  
Finger Protein ◽  
Dna Motif

Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys2His2 zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence.

scholarly journals A Trypanosoma cruzi Zinc Finger protein that controls expression of epimastigote specific genes and affects metacyclogenesis

2020 ◽  
Author(s):  
Thais Silva Tavares ◽  
Fernanda Lins Brandão Mügge ◽  
Viviane Grazielle-Silva ◽  
Bruna Mattioly Valente ◽  
Wanessa Moreira Goes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trypanosoma Cruzi ◽  
Zinc Finger ◽  
Rna Binding ◽  
Environmental Changes ◽  
Zinc Finger Protein ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Control Of Gene Expression ◽  
Genes Encoding

SummaryTrypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and control of gene expression relies on mechanisms acting at the post-transcriptional level. Transcriptome analyses comparing epimastigote, trypomastigote and intracellular amastigote stages revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBP), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP (TcZH3H12) that contains a zinc finger domain, and whose transcripts are upregulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Comparative transcriptome analysis revealed a TcZC3H12-dependent expression of epimastigote specific genes encoding amino acid transporters and proteins associated with differentiation (PAD), among others. RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.

scholarly journals Regulation of epithelial sodium transport by promyelocytic leukemia zinc finger protein

2008 ◽  
Vol 295 (1) ◽  
pp. F18-F26 ◽  
Author(s):  
Anikó Náray-Fejes-Tóth ◽  
Cary Boyd ◽  
Géza Fejes-Tóth
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Negative Regulator ◽  
Sodium Reabsorption ◽  
Target Cells ◽  
Mrna Levels ◽  
Na Transport ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Finger Protein

Aldosterone is the principal regulator of Na homeostasis, and thereby blood pressure. One of the main targets of aldosterone is the epithelial Na channel (ENaC) located in the apical membrane of target cells. Previous studies identified several genes involved in the regulation of ENaC such as SGK1; however, SGK1 knockout mice have only a mild salt-losing phenotype, indicating that further genes must be involved in the action of aldosterone. In our search for further aldosterone-regulated genes, we discovered that aldosterone, at physiological concentrations, induces the expression of the promyelocytic leukemia zinc finger protein (PLZF) in renal cortical collecting duct (CCD) cell lines that stably express mineralocorticoid receptors (MRs). This effect is rapid and does not require de novo protein synthesis, suggesting a direct action. Surprisingly, stable overexpression of human or mouse PLZF isoforms significantly decreased transepithelial Na transport in CCD cells while having no effect on the integrity of the monolayers. In parallel with the decline in Na transport, PLZF suppressed the mRNA levels of β- and γ-ENaC subunits. These observations suggest that PLZF is a negative regulator of ENaC in renal epithelial cells and might be part of a negative feedback loop that limits aldosterone's stimulatory effects on sodium reabsorption.

scholarly journals The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes.

1994 ◽  
Vol 14 (5) ◽  
pp. 3150-3157 ◽  
Author(s):  
K Irie ◽  
K Yamaguchi ◽  
K Kawase ◽  
K Matsumoto
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Signal Transduction Pathway ◽  
Negative Regulator ◽  
Growth Defect ◽  
Recessive Mutation ◽  
Temperature Sensitive ◽  
Pheromone Response Pathway ◽  
Finger Protein ◽  
Putative Zinc Finger

The STE4 gene encodes the beta subunit of a heterotrimeric G protein that is an essential component of the pheromone signal transduction pathway. To identify downstream component(s) of Ste4, we sought pseudo-revertants that restored mating competence to ste4 mutants. The suppressor mot2 was isolated as a recessive mutation that restored conjugational competence to a temperature-sensitive ste4 mutant and simultaneously conferred a temperature-sensitive growth phenotype. The MOT2 gene encodes a putative zinc finger protein, the deletion of which resulted in temperature-sensitive growth, increased expression of FUS1 in the absence of pheromones, and suppression of a deletion of the alpha-factor receptor. On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion. These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway. Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84. Overexpression of MOT2 suppresses the growth defect of temperature-sensitive mutations in CDC36 and CDC39. These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39.

The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes

1994 ◽  
Vol 14 (5) ◽  
pp. 3150-3157
Author(s):  
K Irie ◽  
K Yamaguchi ◽  
K Kawase ◽  
K Matsumoto
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Signal Transduction Pathway ◽  
Negative Regulator ◽  
Growth Defect ◽  
Recessive Mutation ◽  
Temperature Sensitive ◽  
Pheromone Response Pathway ◽  
Finger Protein ◽  
Putative Zinc Finger

The STE4 gene encodes the beta subunit of a heterotrimeric G protein that is an essential component of the pheromone signal transduction pathway. To identify downstream component(s) of Ste4, we sought pseudo-revertants that restored mating competence to ste4 mutants. The suppressor mot2 was isolated as a recessive mutation that restored conjugational competence to a temperature-sensitive ste4 mutant and simultaneously conferred a temperature-sensitive growth phenotype. The MOT2 gene encodes a putative zinc finger protein, the deletion of which resulted in temperature-sensitive growth, increased expression of FUS1 in the absence of pheromones, and suppression of a deletion of the alpha-factor receptor. On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion. These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway. Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84. Overexpression of MOT2 suppresses the growth defect of temperature-sensitive mutations in CDC36 and CDC39. These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39.

scholarly journals A Conformational Switch in the Zinc Finger Protein Kaiso Mediates Differential Readout of Specific and Methylated DNA Sequences

Biochemistry ◽  
2020 ◽  
Vol 59 (20) ◽  
pp. 1909-1926
Author(s):  
Evgenia N. Nikolova ◽  
Robyn L. Stanfield ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Zinc Finger ◽  
Dna Sequences ◽  
Zinc Finger Protein ◽  
Conformational Switch ◽  
Methylated Dna ◽  
Finger Protein
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