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Rice (Oryza sativa L.) is highly sensitive to low temperatures, which can significantly reduce its production. Cold tolerance in rice is a complex trait regulated by multiple mechanisms. OsTZF5, a member of the CCCH-type zinc finger gene family in rice, has been previously reported that overexpressing OsTZF5 under the stress-responsive promoter can confer drought resistance. In this study, we showed that the loss of function mutants of OsTZF5 decreased seed germination rate and chilling tolerance in rice, and influencing normal growth and development. OsTZF5 is expressed in various parts of the rice plant, including roots, stems, leaves and inflorescences, with the highest expression levels observed in leaves. Additionally, the expression of OsTZF5 gene was influenced by various stress conditions and hormone treatments. OsTZF5 knock-out mutants exhibited significantly lower survival rates compared to the wild type (Zhonghua11, ZH11) after cold stress, as well as fewer tillers, lower thousand-grain weight, and reduced grain yield under normal conditions. Transcriptomic analyses revealed that the expression of cold stress-related genes was significantly down-regulated in OsTZF5 knock-out mutants compared to ZH11 after cold stress. This down-regulation likely contributes to the reduced cold stress tolerance observed in OsTZF5 knock-out mutants. Our findings suggest that OsTZF5 is a multifunctional gene that plays a crucial role in regulating cold stress in rice.Key message: OsTZF5 participates in chilling tolerance regulation, and serves as an essential growth and development regulator affecting agronomic traits in rice. Further transcriptomic analyses revealed that OsTZF5 positively regulates rice cold tolerance at the seedling stage by influencing the expression of cold stress-related genes. These results suggest that OsTZF5 is a multifunctional gene and provides a new genetic source for cold tolerance in rice. [ABSTRACT FROM AUTHOR]

ZKSCAN3 (also known as ZNF306) plays a pivotal role in the regulation of various cellular processes that are fundamental to the development of cancer. It has been widely acknowledged as a key contributor to cancer progression, with its overexpression consistently reported in a broad spectrum of malignancies. Importantly, clinical studies have demonstrated a significant association between elevated ZKSCAN3 levels and adverse prognosis, as well as resistance to therapeutic drugs. Specifically, ZKSCAN3 promotes tumor progression by enhancing multiple hallmark features of cancer and promoting the acquisition of cancer-specific phenotypes. These effects manifest as increased tumor cell proliferation, invasion, and metastasis, accompanied by inhibiting tumor cell apoptosis and modulating autophagy. Consequently, ZKSCAN3 emerges as a promising prognostic marker, and targeting its inhibition represents a potential strategy for anti-tumor therapy. In this review, we provide an updated perspective on the role of ZKSCAN3 in governing tumor characteristics and the underlying molecular mechanisms. Furthermore, we underscore the clinical relevance of ZKSCAN3 and its potential implications for tumor prognosis and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies. [ABSTRACT FROM AUTHOR]

As the most abundant class of transcription factors in eukaryotes, C2H2-type zinc finger proteins (C2H2-ZFPs) play critical roles in various biological processes. Despite being extensively studied in mammals, C2H2-ZFPs remain poorly characterized in birds. Recent accumulation of multi-omics data for chicken enables the genome-wide investigation of C2H2-ZFPs in birds. The purpose of this study is to reveal the genomic occurrence and evolutionary signature of chicken C2H2-ZFPs, and further depict their expression profiles across diverse chicken tissues. Here, we annotated 301 C2H2-ZFPs in chicken genome, which are associated with different effector domains, including KRAB, BTB, HOMEO, PHD, SCAN, and SET. Among them, most KRAB-ZFPs lack orthologues in mammals and tend to form clusters by duplication, supporting their fast evolution in chicken. We also annotated a unique and previously unidentified SCAN-ZFP, which is lineage-specific and highly expressed in ovary and testis. By integrating 101 RNA-seq datasets for 32 tissues, we found that most C2H2-ZFPs have tissue-specific expression. Particularly, 74 C2H2-ZFPs—including 27 KRAB-ZFPs—show blastoderm-enriched expression, indicating their association with early embryo development. Overall, this study performs comprehensive annotation and expression profiling of C2H2 ZFPs in diverse chicken tissues, which gives new insights into the evolution and potential function of C2H2-ZFPs in avian species. [ABSTRACT FROM AUTHOR]

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Abstract Clear cell renal cell carcinoma (ccRCC), with high mortality and poor prognosis, is the most common type of renal malignancy. It is necessary to identify new biomarkers that can serve as indicators for the detection of ccRCC at its early stages. In this study, we analyzed the role of classical zinc finger protein 692 (ZNF692) in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and Single Cell Portal and immunohistochemical (IHC) staining of a tissue-microarray, and analyzed the function of ZNF692 in ccRCC cells. The analyses indicated that ZNF692 was upregulated in ccRCC samples compared with normal or paracancerous control samples (P

Huntington's disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) resulting in expression of mutant HTT proteins (mHTT) with extended polyglutamine tracts, including in striatal neurons and astrocytes. It is unknown whether pathophysiology in vivo can be attenuated by lowering mHTT in either cell type throughout the brain, and the relative contributions of neurons and astrocytes to HD remain undefined. We use zinc finger protein (ZFP) transcriptional repressors to cell-selectively lower mHTT in vivo. Astrocytes display loss of essential functions such as cholesterol metabolism that are partly driven by greater neuronal dysfunctions, which encompass neuromodulation, synaptic, and intracellular signaling pathways. Using transcriptomics, proteomics, electrophysiology, and behavior, we dissect neuronal and astrocytic contributions to HD pathophysiology. Remarkably, brain-wide delivery of neuronal ZFPs results in strong mHTT lowering, rescue of HD-associated behavioral and molecular phenotypes, and significant extension of lifespan, findings that support translational development.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription‐quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3‐II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3‐II expression. In a xenograft mouse model, tumors formed by MIA PaCa‐2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa. [ABSTRACT FROM AUTHOR]

At present, there are a variety of different approaches to the targeted regulation of gene expression. However, most approaches are devoted to the activation of gene transcription, and the methods for gene silencing are much fewer in number. In this review, we describe the main systems used for the targeted suppression of gene expression (including RNA interference (RNAi), chimeric transcription factors, chimeric zinc finger proteins, transcription activator-like effectors (TALEs)-based repressors, optogenetic tools, and CRISPR/Cas-based repressors) and their application in eukaryotes—plants and animals. We consider the advantages and disadvantages of each approach, compare their effectiveness, and discuss the peculiarities of their usage in plant and animal organisms. This review will be useful for researchers in the field of gene transcription suppression and will allow them to choose the optimal method for suppressing the expression of the gene of interest depending on the research object. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC), with high mortality and poor prognosis, is the most common type of renal malignancy. It is necessary to identify new biomarkers that can serve as indicators for the detection of ccRCC at its early stages. In this study, we analyzed the role of classical zinc finger protein 692 (ZNF692) in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and Single Cell Portal and immunohistochemical (IHC) staining of a tissue-microarray, and analyzed the function of ZNF692 in ccRCC cells. The analyses indicated that ZNF692 was upregulated in ccRCC samples compared with normal or paracancerous control samples (P < 0.001) and that the expression of this gene was linked to poor overall survival (HR = 2.1, P < 0.0001). The knockdown of ZNF692 inhibited the proliferation and migration of ccRCC cells by target GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2), and transmembrane 9 superfamily member 2 (TM9SF2)). T, B, proximal, and collecting tubule cells are the dominant cell types in normal kidney tissue where ZNF692 is expressed. In addition, immune checkpoint blockade (ICB) therapy dramatically changed the expression patterns of ZNF692. Collectively, these data indicate that ZNF692 may serve as prognosis, and as a potential indicator of the response to ICB therapy, a possibility needs to be verified by a case‒control study. [ABSTRACT FROM AUTHOR]

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts. [ABSTRACT FROM AUTHOR]

Purpose: Non-small cell lung cancer (NSCLC) is a complex disease that remains a major public health concern worldwide. One promising avenue for NSCLC treatment is the targeting of transcription factors that regulate key pathways involved in cancer progression. In this study, we investigated the role of the transcription factor ZNF263 in NSCLC and its impact on the regulation of IL33, apoptosis, and autophagy. Methods: Levels of ZNF263 in tissues and cell lines were identified, after which the effects of its knockdown on cellular malignant behaviors, apoptosis and autophagy were assessed. Based on bioinformatics analysis, ZNF263 was found to bind to IL33 promoter, their mutual relationship was confirmed, as well as the role of IL33 in the regulation of ZNF263. The involvement of ZNF263 in the growth of xenograft tumors was assessed using tumor-bearing nude mouse models. Results: Experimental results revealed that ZNF263 was upregulated in NSCLC tissue samples and cell lines. Its expression level is positively correlated with cellular malignant behaviors. We further demonstrated that ZNF263 upregulated IL33 expression, which, in turn, promoted the proliferation and migration, inhibited apoptosis and autophagy in NSCLC cells. Furthermore, ZNF263 knockdown reduced the growth of xenograft tumors in nude mice. Conclusion: This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin-binding patterns, likely due to interactions with various specificity factors. Previously, we showed that the chromatin-binding pattern of the HP1 protein Rhino, a crucial factor of the Drosophila PIWI-interacting RNA (piRNA) pathway, is largely defined by a DNA sequence-specific C2H2 zinc finger protein named Kipferl (Baumgartner et al., 2022). Here, we elucidate the molecular basis of the interaction between Rhino and its guidance factor Kipferl. Through phylogenetic analyses, structure prediction, and in vivo genetics, we identify a single amino acid change within Rhino’s chromodomain, G31D, that does not affect H3K9me2/3 binding but disrupts the interaction between Rhino and Kipferl. Flies carrying the rhinoG31D mutation phenocopy kipferl mutant flies, with Rhino redistributing from piRNA clusters to satellite repeats, causing pronounced changes in the ovarian piRNA profile of rhinoG31D flies. Thus, Rhino’s chromodomain functions as a dual-specificity module, facilitating interactions with both a histone mark and a DNA-binding protein.

Vibrio harveyi is a major pathogen in yellow drum (Nibea albiflora) aquaculture, causing significant mortality and economic losses. In this study, using the latest assembled reference genome of yellow drum by our laboratory, we conducted genome-wide association study (GWAS) analysis on 345 individuals (197 susceptible and 148 resistant). The analysis revealed 24 significant single nucleotide polymorphisms (SNPs) on chromosome 24 within a 217 Kb region. The estimated heritability for all genome-wide SNPs was 0.3578, while the heritability for the 24 significant SNPs was 0.0710. Four candidate genes were identified within this region: Suppressor of Cytokine Signaling 1 (SOCS1), C-type Lectin Domain Family 16A (CLEC16A), Major Histocompatibility Complex Class II Transactivator (CIITA), and Protein Kinase Cβ (PRKCB). Subsequently, expression quantitative trait loci (eQTL) analysis was performed on transcriptome sequencing data from spleen tissues of 78 individuals from the resistant group. On average, each chromosome harbored 49,396 eQTL loci, with an average of one SNP regulate 1.3 genes. Notably, 22.79% of SNPs showed significant associations with the expression of one or more genes. By integrating GWAS and eQTL data, seven SNPs were identified to have significant associations with regulated genes in the eQTL results. All seven SNPs were found to target the same gene, namely Zinc Finger Protein yd23210 in yellow drum. This study provides genetic markers and candidate genes for molecular breeding of yellow drum against V. harveyi infection, offering insights into the molecular immune mechanisms and potential pathways for genetic improvement of disease resistance traits in this species.

Cotton is one of the most important natural fibers used in the textile industry worldwide. It is important to identify the key factors involved in cotton fiber development. In this study, zinc finger protein8 (GhZFP8) encoding a C2H2 transcription factor (TF) was cloned from cotton. qPCR showed that the transcripts of GhZFP8 in cotton were detected in the leaves and fibers at 3, 6, and 30 days post-anthesis (DPA), but not in the roots, stems, or flowers. The overexpression of GhZFP8 increased the trichome number on the siliques, leaves, and inflorescence, but inhibited the growth. The expression of trichome development and cell-elongation-related genes decreased obviously in GhZFP8 overexpressor Arabidopsis. Indole-3-acetic acid (IAA) and 1-Aminocyclopropanecarboxylic acid (ACC) contents were much higher in GhZFP8 overexpressors than that found in the wild type, but the gibberellin (GA) content was lower. The interference of GhZFP8 in cotton caused smaller bolls and shorter fibers than that of the control. The results of DNA affinity purification (DAP)-seq showed that GhZFP8 could bind to the promoter, exon, intron, and intergenic region of the target genes, which are involved in photosynthesis, signal transduction, synthesis of biomass, etc. Our findings implied that GhZFP8 processed multiple biological functions and regulated the development of cotton fiber. [ABSTRACT FROM AUTHOR]

The protist pathogen Plasmodiophora brassicae hijacks the metabolism and development of host cruciferous plants and induces clubroot formation, but little is known about its regulatory mechanisms. Previously, the Pnit2int2 sequence, a sequence around the second intron of the nitrilase gene (BrNIT2) involved in auxin biosynthesis in Brassica rapa ssp. pekinensis, was identified as a specific promoter activated during clubroot formation. In this study, we hypothesized that analysis of the transcriptional regulation of Pnit2int2 could reveal how P. brassicae affects the host gene regulatory system during clubroot development. By yeast one-hybrid screening, the pathogen zinc finger protein PbZFE1 was identified to specifically bind to Pnit2int2. Specific binding of PbZFE1 to Pnit2int2 was also confirmed by electrophoretic mobility shift assay. The binding site of PbZFE1 is essential for promoter activity of Pnit2int2 in clubbed roots of transgenic Arabidopsis thaliana (Pnit2int2-2:: GUS), indicating that PbZFE1 is secreted from P. brassicae and functions within plant cells. Ectopic expression of PbZEF1 in A. thaliana delayed growth and flowering time, suggesting that PbZFE1 has significant impacts on host development and metabolic systems. Thus, P. brassicae appears to secrete PbZFE1 into host cells as a transcription factor-type effector during pathogenesis. [ABSTRACT FROM AUTHOR]

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.

Abstract Background Melanin plays important roles in morphological development, survival, host–pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. Results We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. Conclusions Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

In Drosophila, a large group of actively transcribed genes is located in pericentromeric heterochromatin. It is assumed that heterochromatic proteins recruit transcription factors to gene promoters. Two proteins, Ouib and Nom, were previously shown to bind to the promoters of the heterochromatic genes nvd and spok. Interestingly, Ouib and Nom are paralogs of the M1BP protein, which binds to the promoters of euchromatic genes. We have shown that, like M1BP, the Quib and Nom proteins bind to CP190, which is involved in the recruitment of transcription complexes to promoters. Unlike heterochromatic proteins, Ouib and Nom do not interact with the major heterochromatic protein HP1a and bind to euchromatic promoters on polytene chromosomes from the larval salivary glands. The results suggest a new mechanism for the recruitment of transcription factors into the heterochromatic compartment of the nucleus. [ABSTRACT FROM AUTHOR]

Soil salinisation is a significant challenge to banana production worldwide. Studying candidate salt stress response genes can help to elucidate plant salt-tolerant mechanisms and develop stress-tolerant varieties. In this study, the Musa acuminata Zinc finger15 (MaZFP15) gene, which belongs to the CCCH zinc finger transcription factor family from banana, was introduced into Arabidopsis using the CaMV35S promoter. The transgenic lines expressing MaZFP15 showed increased root branching under salt stress with higher chlorophyll pigment content, lower water loss rates and electrolytic leakage with greater relative water content and increased anti-oxidant enzyme activity (SOD, CAT, POD, APX and GR) compared to control lines (with empty vector) and wild type plants. Analyses of malondialdehyde, the final product of lipid peroxidation, indicated less cell membrane damage in the transgenic lines expressing MaZFP15, than in the control plants. The nuclear location of MaZFP and the elevated expression of abscisic acid-responsive element-binding factor 3 in the salt stress-exposed transgenic lines, support MaZFP15 effecting ABA signalling associated transcriptional regulation of plant stress responses. The responses include the activation of antioxidant enzyme systems and promotion of root growth, contributing to salt tolerance. MaZFP15 can be considered a candidate for molecular breeding of crop varieties that can endure high salt levels. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are important for plant defense against fungal attack. As a necrotrophic fungus, Botrytis cinerea can exploit ROS that originated from both sides of the host and pathogen during interaction to facilitate its infestation. Meanwhile, B. cinerea needs to exert an efficient oxidative stress responsive system to balance the intracellular redox state when encountering deleterious ROS levels. However, the machinery applied by B. cinerea to cope with ROS remains obscure. Herein, we investigated the role of the transcription factor BcMsn2 in regulating B. cinerea redox homeostasis. Disruption of the BcMsn2 gene severely impaired vegetative growth, sclerotium formation, conidial yield, and fungal virulence. The intracellular oxidative homeostasis of the Δbcmsn2 mutant was disrupted, leading to significantly elevated levels of ROS and reduced activities of enzymes closely associated with oxygen stress, such as catalase (CAT) and superoxide dismutase (SOD). RNA-Seq and qRT-PCR analyses showed remarkable downregulation of the expression of several genes encoding ROS scavenging factors involved in maintaining the redox homeostasis in Δbcmsn2, suggesting that BcMsn2 functions as a transcriptional regulator of these genes. Our findings indicated that BcMsn2 plays an indispensable role in maintaining the equilibrium of the redox state in B. cinerea, and intracellular ROS serve as signaling molecules that regulate the growth, asexual reproduction, and virulence of this pathogen. [ABSTRACT FROM AUTHOR]

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The human zinc finger protein 521 (ZNF521) is a co-transcriptional factor with multiple recognized regulatory functions in a range of normal, cancer and stem cell compartments. ZNF521 regulates proliferation, progression and CSC (cancer stem cell) compartments in human ovarian cancer (hOC), which is a very aggressive and late-diagnosed female tumor. Two other important regulators of hOC are the NRF2 and NOTCH signaling pathways. In the present paper, the mRNA and protein levels of ZNF521 were correlated with those of the NRF2-NOTCH signaling components in two different hOC cell lines and in a public dataset of 381 hOC patients. The data show that high levels of ZNF521 significantly increase NRF2-NOTCH signaling expression; conversely, the silencing of ZNF521 impairs NRF2-NOTCH signaling. This experimental work shows that, in hOC, different levels of ZNF521 modulate the NRF2-NOTCH signaling pathway and also influences hOC CSC properties. [ABSTRACT FROM AUTHOR]

Kojic acid (KA) is a valuable secondary metabolite that is regulated by zinc finger proteins in Aspergillus oryzae. However, only two such proteins have been characterized to function in kojic acid production of A. oryzae to date. In this study, we identified a novel zinc finger protein, AoZFA, required for kojic acid biosynthesis in A. oryzae. Our results showed that disruption of AozfA led to increased expression of kojA and kojR involved in kojic acid synthesis, resulting in enhanced kojic acid production, while overexpression of AozfA had the opposite effect. Furthermore, deletion of kojR in the AozfA disruption strain abolished kojic acid production, whereas overexpression of kojR enhanced it, indicating that AoZFA regulates kojic acid production by affect ing kojR. Transcriptional activation assay revealed that AoZFA is a transcriptional activator. Interestingly, when kojR was overexpressed in the AozfA overexpression strain, the production of kojic acid failed to be rescued, suggesting that AozfA plays a distinct role from kojR in kojic acid biosynthesis. Moreover, we found that AozfA was highly induced by zinc during early growth stages, and its overexpression inhibited the growth promoted by zinc, whereas its deletion had no effect, suggesting that AoZFA is nonessential but has a role in the response of A. oryzae to zinc. Overall, these findings provide new insights into the roles of zinc finger proteins in the growth and kojic acid production of A. oryzae. [ABSTRACT FROM AUTHOR]

The Zinc finger protein (ZFP) family is widely distributed in eukaryotes and interacts with DNA, RNA, and various proteins to participate in many molecular processes. In the present study, the biological functions of eight ZFP genes in the lytic cycle and the pathogenicity of Toxoplasma gondii were examined using the CRISPR-Cas9 system. Immunofluorescence showed that four ZFPs (RH248270-HA, RH255310-HA, RH309200-HA, and RH236640-HA) were localized in the cytoplasm, and one ZFP (RH273150-HA) was located in the nucleus, while the expression level of RH285190-HA, RH260870-HA, and RH248450-HA was undetectable. No significant differences were detected between seven RHΔzfp strains (RHΔ285190, RHΔ248270, RHΔ260870, RHΔ255310, RHΔ309200, RHΔ248450, and RHΔ236640) and the wild-type (WT) strain in the T. gondii lytic cycle, including plaque formation, invasion, intracellular replication, and egress, as well as in vitro virulence (p > 0.05). However, the RHΔ273150 strain exhibited significantly lower replication efficiency compared to the other seven RHΔzfp strains and the WT strain, while in vivo virulence in mice was not significantly affected. Comparative expression analysis of the eight zfp genes indicates that certain genes may have essential functions in the sexual reproductive stage of T. gondii. Taken together, these findings expand our current understanding of the roles of ZFPs in T. gondii. [ABSTRACT FROM AUTHOR]

Trichomes provide an excellent model for studying cell differentiation and proliferation. The aboveground tissues of plants with long dense trichomes (LDTs) can cause skin itching in people working in a zucchini field, in which management, pollination, and fruit harvesting are difficult. In this study, an F2 population was constructed with the LDT inbred line "16" and the sparse micro trichome (SMT) inbred line "63" for QTL analysis of type I and II trichome density. Two QTLs were identified on chromosomes 3 and 15 using the QTL-seq method. Additionally, 191 InDel markers were developed on 20 chromosomes, a genetic map was constructed for QTL mapping, and three QTLs were identified on chromosomes 3, 6, and 15. Two QTLs, CpTD3.1 and CpTD15.1, were identified in both QTL-seq and genetic map-based QTL analyses, and CpTD15.1 was the major-effect QTL. The stability of CpTD3.1 and CpTD15.1 was confirmed using data from F2 plants under different environmental conditions. The major-effect QTL CpTD15.1 was located between markers chr15-4991349 and chr15-5766791, with a physical distance of 775.44 kb, and explained 12.71%-29.37% of the phenotypic variation observed in the three environments. CpTD3.1 was located between markers chr3-218350 and chr3-2891236, in a region with a physical distance of 2,672.89 kb, and explained 5.00%-10.64% of the phenotypic variation observed in the three environments. The functional annotations of the genes within the CpTD15.1 region were predicted, and five genes encoding transcription factors regulating trichome development were selected. Cp4.1LG15g04400 encoded zinc finger protein (ZFP) and harbored nonsynonymous SNPs in the conserved ring finger domain between the two parental lines. There were significant differences in Cp4.1LG15g04400 expression between "16" and "63", and a similar pattern was found between germplasm resources of LDT lines and SMT lines. It was presumed that Cp4.1LG15g04400 might regulate trichome density in zucchini. These results lay a foundation for better understanding the density of multicellular nonglandular trichomes and the regulatory mechanism of trichome density in zucchini. [ABSTRACT FROM AUTHOR]

Zinc is a transition metal that displays wide physiological implications ranging from participation in hundreds of enzymes and proteins to normal growth and development. In the reproductive tract of both sexes, zinc maintains a functional role in spermatogenesis, ovulation, fertilization, normal pregnancy, fetal development, and parturition. In this work, we review evidence to date regarding the importance of zinc in oocyte maturation and development, with emphasis on the role of key zinc-binding proteins, as well as examine the effects of zinc and reactive oxygen species (ROS) on oocyte quality and female fertility. We summarize our current knowledge about the participation of zinc in the developing oocyte bound to zinc finger proteins as well as loosely bound zinc ion in the intracellular and extracellular environments. These include aspects related to (1) the impact of zinc deficiency and overwhelming production of ROS under inflammatory conditions on the offset of the physiological antioxidant machinery disturbing biomolecules, proteins, and cellular processes, and their role in contributing to further oxidative stress; (2) the role of ROS in modulating damage to proteins containing zinc, such as zinc finger proteins and nitric oxide synthases (NOS), and expelling the zinc resulting in loss of protein function; and (3) clarify the different role of oxidative stress and zinc deficiency in the pathophysiology of infertility diseases with special emphasis on endometriosis-associated infertility. [ABSTRACT FROM AUTHOR]

Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic modifications of gene expression and function. Acting as important transcriptional regulators of normal biological processes, zinc finger proteins also play key roles in regulating the cellular mechanisms underlying colorectal neoplasia. These actions impact cell differentiation and proliferation, epithelial–mesenchymal transition, apoptosis, homeostasis, senescence, and maintenance of stemness. With the goal of highlighting promising points of therapeutic intervention, we review the oncogenic and tumor suppressor roles of zinc finger proteins with respect to colorectal cancer tumorigenesis and progression. [ABSTRACT FROM AUTHOR]

Osmanthus fragrans is a popular ornamental and odorant plant with high commercial value, but its cultivation and exploitation are limited by low temperature. The ZAT (zinc finger of Arabidopsis thaliana) genes as a subclass of the C2H2-type zinc finger proteins (C2H2-ZFP) family play essential roles in various abiotic stresses. However, their roles in cold stress response in O. fragrans remain unclear. This study identified 38 OfZATs, which could be divided into 5 subgroups based on the phylogenetic tree, with OfZATs in the same subgroup harboring similar gene structures and motif patterns. In addition, 49 segmental and 5 tandem duplication events were detected among OfZAT genes, while some OfZAT genes exhibited specific expression patterns in different tissues. Furthermore, two OfZATs were induced in salt stress and eight OfZATs responded to cold stress. Interestingly, OfZAT35 showed a continuously increasing expression trend under cold stress, while its protein showed nucleus localization with no transcriptional activation activity. Transiently transformed tobacco overexpressing OfZAT35 exhibited a significantly higher relative electrolyte leakage (REL) level and increased activities of superoxide dismutase (SOD), peroxidase (POD), and Ascorbate peroxidase (APX), while there was significantly decreased activity of catalase (CAT). Moreover, CAT, DREB3, and LEA5, which are associated with cold stress, were dramatically decreased after cold treatment in transiently transformed tobacco, suggesting that overexpression of OfZAT35 negatively regulated cold stress. This study provides a basis for exploring the roles of ZAT genes and contributes to uncovering the mechanism of ZAT-mediated cold stress response in O. fragrans. [ABSTRACT FROM AUTHOR]

Zinc finger proteins specifically recognize DNA sequences and, therefore, play a crucial role in living organisms. In this study the Zn(II)-, and DNA-binding of 1MEY#, an artificial zinc finger protein consisting of three finger units was characterized by multiple methods. Fluorimetric, circular dichroism and isothermal calorimetric titrations were applied to determine the accurate stability constant of a zinc finger protein. Assuming that all three zinc finger subunits behave identically, the obtained thermodynamic data for the Zn(II) binding were ΔHbinding site = − (23.5 − 28.0) kcal/mol (depending on the applied protonation state of the cysteines) and logβ'pH 7.4 = 12.2 ± 0.1, being similar to those of the CP1 consensus zinc finger peptide. The specific DNA binding of the protein can be characterized by logβ'pH 7.4 = 8.20 ± 0.08, which is comparable to the affinity of the natural zinc finger proteins (Sp1, WT1, TFIIIA) toward DNA. This value is ~ 1.9 logβ' unit higher than those determined for semi- or nonspecific DNA binding. Competitive circular dichroism and electrophoretic mobility shift measurements revealed that the conditional stability constant characteristic for Zn(II) binding of 1MEY# protein increased by 3.4 orders of magnitude in the presence of its target DNA sequence. [ABSTRACT FROM AUTHOR]

Pitaya (Hylocereus polyrhizus) is cultivated in a broad ecological range, due to its tolerance to drought, heat, and poor soil. The zinc finger proteins regulate gene expression at the transcriptional and post-transcriptional levels, by interacting with DNA, RNA, and proteins, to play roles in plant growth and development, and stress response. Here, a total of 81 CCCH-type zinc finger protein genes were identified from the pitaya genome. Transcriptomic analysis showed that nine of them, including HuTZF3, responded to both salt and heat stress. RT-qPCR results showed that HuTZF3 is expressed in all tested organs of pitaya, with a high level in the roots and stems, and confirmed that expression of HuTZF3 is induced by salt and heat stress. Subcellular localization showed that HuTZF3 is targeted in the processing bodies (PBs) and stress granules (SGs). Heterologous expression of HuTZF3 could improve both salt and heat tolerance in Arabidopsis, reduce oxidative stress, and improve the activity of catalase and peroxidase. Therefore, HuTZF3 may be involved in post-transcriptional regulation via localizing to PBs and SGs, contributing to both salt and heat tolerance in pitaya. [ABSTRACT FROM AUTHOR]

Cotton is one of the most important natural fibers used in the textile industry worldwide. It is important to identify the key factors involved in cotton fiber development. In this study, zinc finger protein8 (GhZFP8) encoding a C2H2 transcription factor (TF) was cloned from cotton. qPCR showed that the transcripts of GhZFP8 in cotton were detected in the leaves and fibers at 3, 6, and 30 days post-anthesis (DPA), but not in the roots, stems, or flowers. The overexpression of GhZFP8 increased the trichome number on the siliques, leaves, and inflorescence, but inhibited the growth. The expression of trichome development and cell-elongation-related genes decreased obviously in GhZFP8 overexpressor Arabidopsis. Indole-3-acetic acid (IAA) and 1-Aminocyclopropanecarboxylic acid (ACC) contents were much higher in GhZFP8 overexpressors than that found in the wild type, but the gibberellin (GA) content was lower. The interference of GhZFP8 in cotton caused smaller bolls and shorter fibers than that of the control. The results of DNA affinity purification (DAP)-seq showed that GhZFP8 could bind to the promoter, exon, intron, and intergenic region of the target genes, which are involved in photosynthesis, signal transduction, synthesis of biomass, etc. Our findings implied that GhZFP8 processed multiple biological functions and regulated the development of cotton fiber.

• Overexpression of GpZF improve drought tolerance in transgenic grass pea. • Antioxidant enzymes activity in transgenic lines was higher than the wild-type plants. • GpZF was without QALGGH motif in grass pea. The genes encoding Cys2/His2-type zinc finger proteins constitute a large family in higher plants consisting of a family of plant transcription factors. GpZF encodes a Cys2/His2-type zinc finger protein. This study identified a novel zinc finger transcription factor gene(GpZF) in the grass pea (Lathyrus sativus L.) involved in response to drought stress. GpZF was cloned in grass pea, and relative gene expression analysis showed that the GpZF gene in independent transgenic lines was more under mild and severe treatments (50% and 25% field capacity-FC). Furthermore, GpZF overexpressing grass pea results in more relative water content, free proline, soluble sugars, and chlorophyll content than the wild-type (WT) plants under 50% and 25% FC stresses, suggesting that this gene may improve drought tolerance by stress-responsive genes. Moreover, after exposure to drought stress, transgenic plants decreased malondialdehyde (MDA) and H 2 O 2 content by increasing significant enzymatic antioxidant activities. The GpZF overexpression has resulted in higher antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), and ascorbate peroxidase (APX)) of transgenic plants than those of the WT plants. Furthermore, in 25% FC, the independent transgenic lines revealed higher survival rates and dry weight than the WT plants. In conclusion, GpZF positively affects drought stress tolerance in Lathyrus sativus. [ABSTRACT FROM AUTHOR]

With Intact Transition Epitope Mapping-Thermodynamic Weak-force Order (ITEM-TWO) analysis in combination with molecular modeling, the phosphorylation-dependent molecular recognition motif of the anti-HpTGEKP antibody has been investigated with binary and ternary component mixtures consisting of antibody and (phospho-) peptides. Amino acid sequences have been selected to match either the antibody's recognition motif or the cancer-related zinc finger protein mutations and phosphorylations of the respective amino acid residues. Upon electrospraying of all the components of the mixtures, that is, hexapeptides, antibody, and intact immune complexes, the produced ions were subjected to mass spectrometric mass filtering. The antibody ions as well as the immune complex ions traversed into the mass spectrometer's collision chamber, whereas paths of unbound peptide ions were blocked prior to entering the collision cell. After dissociation of the multiply charged immune complexes in the gas phase, the complex-released peptide ions were recorded after having traversed the second mass filter. Complex-released peptides were unambiguously identified by their masses using mass analysis with isotope resolution. From the results of our studies with seven (phospho-) peptides with distinct amino acid sequences, which resembled either the antibody's binding motif or mutations, we conclude the following: (i) A negatively charged phospho group, located near the peptide's N-terminus is mandatory for antibody binding when placed on the peptide surface at a precise distance to the C-terminally located positively charged ε-amino group of a lysinyl residue. (ii) A bulky amino acid residue, such as the tyrosinyl residue at the N-terminal position of the (phospho-) threoninyl residue, abolishes antibody binding. (iii) Two closely spaced phospho groups negatively interfere with the surface polarity pattern and abolish antibody binding as well. (iv) Non-phosphorylated peptides are not binding partners of the anti-HpTGEKP antibody. [ABSTRACT FROM AUTHOR]

The Zinc finger protein (ZFP) family is widely distributed in eukaryotes and interacts with DNA, RNA, and various proteins to participate in many molecular processes. In the present study, the biological functions of eight ZFP genes in the lytic cycle and the pathogenicity of Toxoplasma gondii were examined using the CRISPR-Cas9 system. Immunofluorescence showed that four ZFPs (RH248270-HA, RH255310-HA, RH309200-HA, and RH236640-HA) were localized in the cytoplasm, and one ZFP (RH273150-HA) was located in the nucleus, while the expression level of RH285190-HA, RH260870-HA, and RH248450-HA was undetectable. No significant differences were detected between seven RHΔzfp strains (RHΔ285190, RHΔ248270, RHΔ260870, RHΔ255310, RHΔ309200, RHΔ248450, and RHΔ236640) and the wild-type (WT) strain in the T. gondii lytic cycle, including plaque formation, invasion, intracellular replication, and egress, as well as in vitro virulence (p > 0.05). However, the RHΔ273150 strain exhibited significantly lower replication efficiency compared to the other seven RHΔzfp strains and the WT strain, while in vivo virulence in mice was not significantly affected. Comparative expression analysis of the eight zfp genes indicates that certain genes may have essential functions in the sexual reproductive stage of T. gondii. Taken together, these findings expand our current understanding of the roles of ZFPs in T. gondii.

Abstract Zinc finger proteins are transcription factors with the finger domain, which plays a significant role in gene regulation. As the largest family of transcription factors in the human genome, zinc finger (ZNF) proteins are characterized by their different DNA binding motifs, such as C2H2 and Gag knuckle. Different kinds of zinc finger motifs exhibit a wide variety of biological functions. Zinc finger proteins have been reported in various diseases, especially in several cancers. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide, especially in China. Most of HCC patients have suffered from hepatitis B virus (HBV) and hepatitis C virus (HCV) injection for a long time. Although the surgical operation of HCC has been extremely developed, the prognosis of HCC is still very poor, and the underlying mechanisms in HCC tumorigenesis are still not completely understood. Here, we summarize multiple functions and recent research of zinc finger proteins in HCC tumorigenesis and progression. We also discuss the significance of zinc finger proteins in HCC diagnosis and prognostic evaluation.

UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ-/- mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ-/- mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ-/- mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ-/- mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20.IMPORTANCE HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity in vitro and viral pathogenesis in vivo.

Hematopoiesis is a highly coordinated process that generates all the body's blood cells, and perturbations in embryonic hematopoiesis may result in illnesses ranging from fetal anemia to various leukemias. Correct establishment of hematopoietic progenitor cell fate is essential for the development of adequate blood cell subpopulations, although regulators of cell fate commitment have not been fully defined. Here, we show that primary erythropoiesis and myelopoiesis in zebrafish embryos are synergistically regulated by blf and the drl cluster, as simultaneous depletion led to severe erythrocyte aplasia and excessive macrophage formation at the expense of neutrophil development. Integrative analysis of transcriptome- and genome-wide binding data revealed that blf and drl cluster genes are responsible for constraining the expression of vasculogenesis-promoting genes in the intermediate cell mass and monocytopoiesis-promoting genes in the rostral blood island. This indicates that blf and drl cluster genes act as determinants of the fate commitment of erythroid and myeloid progenitor cells. Furthermore, a rescue screen demonstrated that Zfp932 is a potential mammalian functional equivalent to zebrafish blf and drl cluster genes. Our data provide insight into conserved cell fate commitment mechanisms of primitive hematopoiesis. [ABSTRACT FROM AUTHOR]

The chestnut is widely cultivated fruit tree enriched with nutrients and has pleasant tasting fruit. The starch properties of kernels greatly influence the nutritional quality of chestnuts. Although various studies have examined the production and accumulation of starch in chestnuts, the transcription alteration linked with starch properties in the kernels has not yet been fully assessed. The present study was conducted to compare transcriptomic variation and starch profiling of three chestnut cultivars: "Garrone rosso" (eur), Castanea sativa Mill., native to Europe; "Dahongpao" (dhp) and "Jiandingyouli" (jdy), and Castanea mollissima Bl., native to China. The results revealed that "dhp" and "jdy" had higher amylose, amylopectin and total starch content than "eur". Based on transcriptome data, we screened 63.17G clean bases, and detected numerous differentially expressed genes (DEGs) that were associated with starch and sucrose metabolism. Through the combined transcriptomic and starch profiling analysis showed that DEGs in "the starch and sucrose metabolism", "bZIP transcriptional factors", and "zinc finger protein" pathways were positively correlated with starch accumulation, genes encoding sucrose synthase (CMHBY215664 and CMHBY203813), USPase (CMHBY206855), and PGI (CMHBY200699) were found to participate in the biosynthesis, transport, and regulation of starch according to their expression patterns in chestnut kernels. Furthermore, genes encoding different transcription factors (ERF, bZIP, MYB, and WRKY) that potentially regulate the expression of genes involved in starch and sucrose metabolism were selected by coexpression analysis, which highlighted that most MYB and WRKY TF members were positively correlated with starch synthase (SS). qRT-PCR assay results of nine selected DEGs confirmed the accuracy of the RNA-Seq data. Our results provide insights into genetic resources for deciphering the molecular mechanisms of chestnut starch accumulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: RNA interference (RNAi) has potential application in pest control, and selection of the specific target gene is one of the key steps in RNAi. As an important effector, the zinc finger protein (ZFP) gene has high similarity among aphid species, and may have potential use in an RNAi‐based pest control strategy. This study assessed the control efficiency of an RNAi target, MPZC3H10, a CCCH‐type ZFP gene, against green peach aphid. RESULTS: ZC3H10 amino acid sequence similarity is more than 97.71% among the five tested aphid species: Myzus persicae, Aphis citricidus, Acyrthosiphon pisum, Diuraphis noxia and Rhopalosiphum maidis. However, no homologous sequence was found in the transcriptome of their ladybeetle predator, Propylaea japonica. Spatial expression patterns revealed that MPZC3H10 showed high expression in the muscle and fat body of M. persicae. The RNAi bioassay revealed that silencing of MPZC3H10 resulted in high mortality (53.33%) in M. persicae. By contrast, there were no observed negative effects on the growth and development of P. japonica when fed on aphids treated with double‐stranded RNA (dsRNA) or injected with a "high dose" of dsRNA. CONCLUSION: Targeting MPZC3H10 showed promising efficiency for green peach aphid control via artificially designed dsRNA, and was safe for the predatory ladybeetle. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the inhibition of artesunate on growth of transplanted human gastric cancer through Toll-like receptor ( TLR) 4 / nuclear factor κB (NF-κB) signaling pathway and its effects on expression of proliferating cell nuclear antigen (PNCA) and ZNF139. METHODS: Forty BALB / c nude mice were inoculated with human gastric cancer cell line SGC7901 for modeling and randomly divided into the model group ( 0. 9% sodium chloride solution), cisplatin group (cisplatin 4 mg / kg), artesunate group (artesunate for injection 100 mg / kg) and combination group ( cisplatin 4 mg / kg+ artesunate for injection 100 mg / kg). Intratumoral injection was performed twice a week for 4 weeks. The appetite, activity, mental state and tumor growth of nude mice were recorded. Hematoxylin and Eosin staining were used for pathological detection, MTT assay was used to detect the growth of primary cells, reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB, and Western blotting was used to detect the relative protein expression. RESULTS: Compared with the model group, the average tumor weight of cisplatin group, artesunate group and combined group decreased significantly;compared with the cisplatin group, the average tumor weight increased and the tumor inhibition rate decreased in the artesunate group;the average tumor weight of the combination group was lower than that of the cisplatin group and artesunate group, and the tumor inhibition rate was higher than that of the cisplatin group and artesunate group, with statistically significant differences (P<0. 05). After 48 h of culture, the OD values of cisplatin group, artesunate group and combination group were lower than those of model group;the OD value of the combination group was lower than that of the cisplatin group and artesunate group, and the inhibition rate was higher than that of the cisplatin group and artesunate group, with statistically significant differences (P<0. 05). Compared with the model group, the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB in the cisplatin group, artesunate group and combination group significantly decreased; the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB of the cisplatin group were significantly lower than those of the artesunate group; the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB of the combination group were significantly lower than those of the cisplatin group and artesunate group, with statistically significant differences ( P < 0. 05 ). CONCLUSIONS: Artesunate may inhibit the growth of human gastric cancer through inhibiting the TLR4/ NF-κB signaling pathway, which can down-regulate the expression of PCNA and ZNF139 and affect the proliferation, invasion and metastasis of tumor. [ABSTRACT FROM AUTHOR]

Rice is an important cereal crop, which provides staple food for more than half of the world’s population. To meet the demand of the ever-growing population in the next few decades, an extra increase in rice yield is an urgent need. Given that various agronomic traits contribute to the yield of rice, deciphering the key regulators involved in multiple agronomic trait formation is particularly important. As a superfamily of transcription factors, zinc finger proteins participate in regulating multiple genes in almost every stage of rice growth and development. Therefore, understanding zinc finger proteins underlying regulatory network would provide insights into the regulation of agronomic traits in rice. To this end, we intend to summarize the current advances in zinc finger proteins, with emphasis on C2H2 and CCCH proteins, and then discuss their potential in improving rice yield. [ABSTRACT FROM AUTHOR]

Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the concentration of zinc finger protein 510 (ZNF510) in the saliva of patients with oral lichen planus and healthy individuals in 2019.Methods: This cross-sectional analytical study was performed on 24 patients with oral lichen planus and 25 healthy individuals referred to the School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, between June and October 2019. In the case group, the severity of lesions was determined according to the Thongprasom index. Unstimulated saliva was collected from the subjects and the samples were examined for the presence of the ZNF510 protein using ELISA method. The data were statistically analyzed through SPSS 23. For data analysis, Kolmogorov-Smirnov test, the independent t-test, the independent samples Kruskal-Wallis test, and one-way analysis of variance were used.Results: This study included 32 females (65.3%), and 17 males (34.7%). The subjects’ age range was between 23-70 years and the mean age of them was 46.26 ± 10.90 years. The mean ZNF510 (ppm) in the case group was 86.12 ± 34.88, while in the control group, it was 46.43 ± 23.32. The two groups were significantly different in terms of the mean ZNF510 (P

Expanded GGGGCC repeats in the first intron of the C9orf72 gene represent the most common cause of familial amyotrophic lateral sclerosis (ALS), but the mechanisms underlying repeat-induced disease remain incompletely resolved. One proposed gain-of-function mechanism is that repeat-containing RNA forms aggregates that sequester RNA binding proteins, leading to altered RNA metabolism in motor neurons. Here, we identify the zinc finger protein Zfp106 as a specific GGGGCC RNA repeat-binding protein, and using affinity purification-mass spectrometry, we show that Zfp106 interacts with multiple other RNA binding proteins, including the ALS-associated factors TDP-43 and FUS. We also show that Zfp106 knockout mice develop severe motor neuron degeneration, which can be suppressed by transgenic restoration of Zfp106 specifically in motor neurons. Finally, we show that Zfp106 potently suppresses neurotoxicity in a Drosophila model of C9orf72 ALS. Thus, these studies identify Zfp106 as an RNA binding protein with important implications for ALS.

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

Osmanthus fragrans is a popular ornamental and odorant plant with high commercial value, but its cultivation and exploitation are limited by low temperature. The ZAT (zinc finger of Arabidopsis thaliana) genes as a subclass of the C2H2-type zinc finger proteins (C2H2-ZFP) family play essential roles in various abiotic stresses. However, their roles in cold stress response in O. fragrans remain unclear. This study identified 38 OfZATs, which could be divided into 5 subgroups based on the phylogenetic tree, with OfZATs in the same subgroup harboring similar gene structures and motif patterns. In addition, 49 segmental and 5 tandem duplication events were detected among OfZAT genes, while some OfZAT genes exhibited specific expression patterns in different tissues. Furthermore, two OfZATs were induced in salt stress and eight OfZATs responded to cold stress. Interestingly, OfZAT35 showed a continuously increasing expression trend under cold stress, while its protein showed nucleus localization with no transcriptional activation activity. Transiently transformed tobacco overexpressing OfZAT35 exhibited a significantly higher relative electrolyte leakage (REL) level and increased activities of superoxide dismutase (SOD), peroxidase (POD), and Ascorbate peroxidase (APX), while there was significantly decreased activity of catalase (CAT). Moreover, CAT, DREB3, and LEA5, which are associated with cold stress, were dramatically decreased after cold treatment in transiently transformed tobacco, suggesting that overexpression of OfZAT35 negatively regulated cold stress. This study provides a basis for exploring the roles of ZAT genes and contributes to uncovering the mechanism of ZAT-mediated cold stress response in O. fragrans.