C2H2-type Zinc Finger Research Articles

NAA enhances armillaria gallica growth by modulating nitrogen metabolism through AgZFP48.

Armillaria gallica (A. gallica) is a fungus with both medicinal and edible properties. Previous transcriptome analysis has identified the C2H2-type zinc finger transcription factor as a candidate gene involved in the NAA-induced growth promotion of A. gallica. However, the molecular mechanism underlying the enhancement of A. gallica growth by C2H2 transcription factor in response to NAA treatment remains unclear. In this study, we identified a C2H2-type zinc finger transcription factor gene in A. gallica and investigated its function, aiming to elucidate the mechanism by which C2H2-type zinc finger transcription factors regulate the growth of A. gallica. We identified and characterized a novel C2H2-type zinc finger transcription factor, AgZFP48, in A. gallica and found that AgZFP48 is located in the nucleus, where it acts as a transcription activator. AgZFP48 positively regulated the growth of A. gallica. The potential targets of AgZFP48 were identified by using DNA affinity purification sequencing (DAP-seq). In addition, four candidate genes were selected for Electrophoretic Mobility Shift Assays (EMSA) and luciferase reporter activity assessment. The results showed that AgZFP48 activated the expression of ammonium transporter (AgAMT), glutamine synthetase (AgGS), acetylornithine aminotransferase (AgAcOAT), and amino acid permease (AgAAP) by binding to their promoters or exons. In summary, our results suggest that AgZFP48 promotes nitrogen metabolism in A. gallica by activating the expression of nitrogen metabolism-related genes, thereby regulating the growth of the fungus.

C2H2 Zinc Finger Protein Family Analysis of Rosa rugosa Identified a Salt-Tolerance Regulator, RrC2H2-8.

Rosa rugosa is a representative aromatic species. Wild roses are known for their strong tolerance to highly salty environments, whereas cultivated varieties of roses exhibit lower salt stress tolerance, limiting their development and industrial expansion. Previous studies have shown that C2H2-type zinc finger proteins play a crucial role in plants' resistance to abiotic stresses. In this study, 102 C2H2-type zinc finger genes (RrC2H2s) were identified in R. rugosa via a comprehensive approach. These genes were categorized into three lineages, and their motif constitutions were grouped into four classes. RrC2H2s were distributed across all seven rose chromosomes, with 15 paralogous gene pairs identified within synteny regions. Additionally, 43 RrC2H2s showed differential expression across various tissues under salt stress, with RrC2H2-8 being the only gene consistently repressed in all tissues. Subcellular localization analysis revealed that the RrC2H2-8 protein was localized in the nucleus. The heterologous expression of RrC2H2-8 in Arabidopsis significantly improved its growth under salt stress compared to the wild-type (WT) plants. Furthermore, the malondialdehyde content in the roots of transgenic Arabidopsis was significantly lower than that in the WT, suggesting that RrC2H2-8 enhanced salt tolerance by reducing cellular damage. This study provides a systematic understanding of the RrC2H2 family and identifies RrC2H2-8 as a regulator of salt tolerance, laying a foundation for future research on the mechanisms of salt stress regulation by RrC2H2.

Genetic Investigation of Regulatory Regions of MKRN3 and DLK1 Genes in Children with Central Precocious Puberty.

Most of the loss-of-function mutations described in children with central precocious puberty (CPP) is located into the coding regions of MKRN3 or DLK1 genes. Notably, potential abnormalities in the regulatory regions of these CPP-genes are rarely explored. To search for pathogenic variants in the regulatory regions of MKRN3 and DLK1 genes in patients with familial or idiopathic CPP. A cohort of 217 individuals with CPP (205 girls and 12 boys; 143 sporadic cases and 74 familial cases) was investigated. Rare and potentially pathogenic variants in the coding regions of both genes were previously excluded. Analyses of the regulatory regions of MKRN3 and DLK1 were performed using polymerase chain reaction and direct automated sequencing (Sanger method). Circulating serum levels of MKRN3 and DLK1 proteins were measured using ELISA assay. We identified a heterozygous allelic variant (c.-265G>A), previously associated with CPP, located in the promoter region of the MKRN3 gene in three girls from two unrelated families. In silico prediction analysis indicated that the c.-265G>A variant was in the ZNF384 binding region. ZNF384 gene encodes a C2H2-type zinc finger protein, which might act as a transcription factor. MKRN3 serum levels varied from 197.5 pg/mL to 1,907 pg/mL and were relatively lower in patients with CPP who carried the c.-265G>A variant. No pathogenic allelic variant was found in the regulatory region of the DLK1 gene. Pathogenic variants in the regulatory region of MKRN3 gene are rare and can be associated with the CPP phenotype.

SUPPRESSOR OF FRIGIDA 4 cooperates with the histone methylation reader EBS to positively regulate root development.

Maintenance and homeostasis of the quiescent center (QC) in Arabidopsis (Arabidopsis thaliana) root apical meristems are critical for stem cell organization and root development. Despite great progress in relevant research, the molecular mechanisms that determine the root stem cell fate and QC still need further exploration. In Arabidopsis, SUPPRESSOR OF FRIGIDA 4 (SUF4) encodes a C2H2-type zinc finger protein that represses flowering by transcriptional activation of FLOWERING LOCUS C (FLC) through the FRIGIDA (FRI) pathway, and EARLY BOLTING IN SHORT DAYS (EBS) is a bivalent histone reader that prevents premature flowering. Here, we found that SUF4 directly interacts with EBS in vivo and in vitro. Loss of function of SUF4 and/or EBS resulted in disorganization of the QC, aberrant cell division, and stunted root growth. RNA-seq and reverse transcription quantitative real-time polymerase chain reaction analysis revealed that SUF4 and EBS coregulate many root development-related genes. A series of biochemical analyses demonstrated that SUF4 directly binds to the promoter of SCARECROW (SCR), which encodes a key regulator of root development. Chromatin immunoprecipitation assay indicated that both SUF4 and EBS are recruited to the SCR locus in an interdependent manner to promote H3K4me3 levels and suppress H3K27me3 levels, thereby activating the expression of SCR. These findings improve our understanding of the function of SUF4 and EBS and provide insights into the molecular mechanism that couples a transcription factor and a histone methylation reader to modulate QC specification and root development in Arabidopsis.

A C2H2-type zinc finger protein TaZFP8-5B negatively regulates disease resistance

BackgroundZinc finger proteins (ZFPs) are important regulators in abiotic and biotic stress tolerance in plants. However, the role of the ZFPs in wheat responding to pathogen infection is poorly understood.ResultsIn this study, we found TaZFP8-5B was down-regulated by Puccinia striiformis f. sp. tritici (Pst) infection. TaZFP8-5B possesses a single C2H2-type zinc finger domain with a plant-specific QALGGH motif, and an EAR motif (LxLxL) at the C-terminus. The EAR motif represses the trans-activation ability of TaZFP8-5B. Knocking down the expression of TaZFP8 by virus-induced gene silencing increased wheat resistance to Pst, whereas TaZFP8-5B-overexpressing reduced wheat resistance to stripe rust and rice resistance to Magnaporthe oryzae, suggesting that TaZFP8-5B plays a negative role in the modulation of plant immunity. Using bimolecular fluorescence complementation, split-luciferase, and yeast two-hybrid assays, we showed that TaZFP8-5B interacted with a wheat calmodulin-like protein TaCML21. Knock-down of TaCML21 reduced wheat resistance to Pst.ConclusionsThis study characterized the function of TaZFP8-5B and its interacting protein TaCML21. Our findings provide a new perspective on a regulatory module made up of TaCML21-TaZFP8-5B in plant immunity.

KNUCKLES regulates floral meristem termination by controlling auxin distribution and cytokinin activity.

The termination of floral meristem (FM) activity is essential for the normal development of reproductive floral organs. During this process, KNUCKLES (KNU), a C2H2-type zinc finger protein, crucially regulates FM termination by directly repressing the expression of both the stem cell identity gene WUSCHEL (WUS) and the stem cell marker gene CLAVATA3 (CLV3) to abolish the WUS-CLV3 feedback loop required for FM maintenance. In addition, phytohormones auxin and cytokinin are involved in FM regulation. However, whether KNU modulates auxin and cytokinin activities for FM determinacy control remains unclear. Here, we show that the auxin distribution and the cytokinin activity mediated by KNU in Arabidopsis (Arabidopsis thaliana) promote the termination of FM during stage 6 of flower development. Mutation of KNU leads to altered distribution of auxin and cytokinin in the FM of a stage 6 floral bud. Moreover, KNU directly represses the auxin transporter gene PIN-FORMED1 (PIN1) and the cytokinin biosynthesis gene ISOPENTENYLTRANSFERASE7 (IPT7) via mediating H3K27me3 deposition on these 2 loci to regulate auxin and cytokinin activities. Our study presents a molecular regulatory network that elucidates how the transcriptional repressor KNU integrates and modulates the activities of auxin and cytokinin, thus securing the timed FM termination.

The C2H2-type zinc finger transcription factor ZmDi19-7 regulates plant height and organ size by promoting cell size in maize.

The drought-induced protein 19 (Di19) gene family encodes a Cys2/His2 zinc-finger protein implicated in responses to diverse plant stressors. To date, potential roles of these proteins as transcription factors remain largely elusive in maize. Here, we show that ZmDi19-7 gene exerts pivotal functions in regulation of plant height and organ growth by modulating the cell size in maize. ZmDi19-7 physically interacts with ubiquitin receptor protein ZmDAR1b, which is indispensable in ubiquitination of ZmDi19-7 and affects its protein stability. Further genetic analysis demonstrated that ZmDAR1b act in a common pathway with ZmDi19-7 to regulate cell size in maize. ZmDi19-7, severing as a transcriptional factor, is significantly enriched in conserved DiBS element in the promoter region of ZmHSP22, ZmHSP18c, ZmSAUR25, ZmSAUR55, ZmSAUR7 and ZmXTH23 and orchestrates the expression of these genes involving in auxin-mediated cell expansion and protein processing in the endoplasmic reticulum. Thus, our findings demonstrate that ZmDi19-7 is an important newfound component of the ubiquitin-proteasome pathway in regulation of plant height and organ size in maize. These discoveries highlight potential targets for the genetic improvement of maize in the future.

ZF protein C2H2-71 regulates soluble solids content by inhibiting LIN5 in tomato

Soluble solids content (SSC) plays an important role in determining the flavor of tomato fruits. Tomato fruit SSC has been shown to be transcriptionally regulated via sugar metabolism. Previous studies have been predominantly focused on the role of C2H2-type zinc finger proteins in tomato growth and development. However, the specific regulatory mechanism of C2H2 in the accumulation of soluble solids in tomato fruits are yet to be fully understood. This study involved the selection of eight tomato accessions with varying levels of SSC to study the expression of SlC2H2 family genes in red ripe fruits. The study found that the levels of SlC2H2-71 expressions were significantly reduced in high-SSC accessions compared to low-SSC accessions. The Slc2h2-71 mutant lines were developed using the CRISPR-Cas9 system, leading to elevated levels of soluble solids, fructose, glucose, malic, and citric acids in mature red ripe fruits. However, sucrose content in the edited Slc2h2-71 mutant lines generally decreased. RNA-seq analysis revealed that fruits from the mutant lines had altered expression of genes related to sugar and acid metabolic pathways, which was further confirmed by quantitative real time PCR. Specifically, there was an observed increase in the expression of SlLIN5 encoding the cell wall invertase (CWIN). The yeast one-hybrid (Y1H) assay, 35S::UAS-GUS, dual-luciferase reporter systems and electrophoretic mobility shift assay (EMSA) demonstrated that SlC2H2-71 regulates tomato sugar metabolism by directly binding to the promoter region of SlLIN5, culminating in the repression of its transcriptional activity. The activity of acid invertase in the SlC2H2-71 knock-out lines exhibited a significantly higher level compared to that observed in the control lines. In summary, the regulation of tomato fruit SSC by SlC2H2-71 involves the inhibition of SlLIN5 expression.

ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a

C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.

A C2H2-Type Zinc Finger Protein from Mentha canadensis, McZFP1, Negatively Regulates Epidermal Cell Patterning and Salt Tolerance

C2H2-type zinc finger protein (C2H2-ZFP) transcription factors play evident roles in regulating plant growth and development and abiotic stress responses. However, the role of C2H2-ZFP from Mentha canadensis remains uncertain. We identified the multifunctional C2H2-ZFP gene McZFP1 from M. canadensis based on phylogenetic analysis. The McZFP1 gene was highly expressed in stems, responding to abiotic stress and phytohormone treatments. McZFP1 localized in the nucleus and showed no transcriptional autoactivation activity in yeast. McZFP1 overexpression in Arabidopsis thaliana significantly reduced the number of trichomes and root hairs, root hair length, and salt stress tolerance. Further study revealed that McZFP1 overexpression increased the expression of negative regulator genes and decreased that of positive regulator genes to inhibit plant trichome and root hair development. Malondialdehyde accumulation was promoted, but the proline content and catalase, superoxide dismutase, and peroxidase activities were reduced and the expression of stress response genes was inhibited in McZFP1 overexpression lines under salt treatment, thereby compromising plant salt tolerance. Overall, these results indicate that McZFP1 is a novel C2H2-ZFP transcription factor that plays negative roles in trichome and root hair development and salt stress tolerance.

AtZAT10/STZ1 improves drought tolerance and increases fiber yield in cotton.

Drought poses a significant challenge to global crop productivity, necessitating innovative approaches to bolster plant resilience. Leveraging transgenic technology to bolster drought tolerance in crops emerges as a promising strategy for addressing the demands of a rapidly growing global populace. AtZAT10/STZ1, a C2H2-type zinc finger protein transcription factor has shown to significantly improve Arabidopsis' tolerance to various abiotic stresses. In this study, we reports that AtSTZ1 confers notable drought resistance in upland cotton (Gossypium hirsutum), amplifying cotton fiber yield under varying conditions, including irrigated and water-limited environments, in field trials. Notably, AtSTZ1-overexpressing transgenic cotton showcases enhanced drought resilience across critical growth stages, including seed germination, seedling establishment, and reproductive phases. Morphological analysis reveals an expanded root system characterized by an elongated taproot system, increased lateral roots, augmented root biomass, and enlarged cell dimensions from transgenic cotton plants. Additionally, higher contents of proline, chlorophyll, soluble sugars, and enhanced ROS-scavenging enzyme activities are observed in leaves of transgenic plants subjected to drought, underscoring improved physiological adaptations. Furthermore, transgenic lines exhibit heightened photosynthetic rate, increased water use efficiency, and larger stomatal and epidermal cell sizes, coupled with a decline in leaf stomatal conductance and density, as well as diminished transpiration rates compared to the wild type counterparts. Transcriptome profiling unveils 106 differentially expressed genes in transgenic cotton leaves post-drought treatment, including protein kinases, transcription factors, aquaporins, and heat shock proteins, indicative of an orchestrated stress response. Collectively, these findings underscore the capacity of AtSTZ1 to augment the expression of abiotic stress-related genes in cotton following drought conditions, thus presenting a compelling candidate for genetic manipulation aimed at enhancing crop resilience.

Comprehensive Annotation and Expression Profiling of C2H2 Zinc Finger Transcription Factors across Chicken Tissues.

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.

The joint toxicity effect of glyphosate and cadmium in a concentration-dependent manner on nematode Caenorhabditis elegans

The co-occurrence of glyphosate (GPS), a commonly used organophosphorus herbicide, and cadmium (Cd), a neurotoxic metal, in agricultural environments prompts concerns about their combined toxic effects on ecosystems. This study explores the combined effects of GPS and Cd on the model organism Caenorhabditis elegans (C. elegans), to understand their cumulative effects in organismal living environments. We investigated the interaction between GPS and Cd over 24 hours using a comprehensive approach that included a variety of toxicity endpoints as well as the novel Automated Recognition and Statistics Tool (NCLE) for body bend measurement. Our data show a concentration-dependent interplay in which antagonistic effects at lower concentrations reduce phenotypic damage while synergistic effects emerge at higher concentrations, particularly at GPS's LC50. Transcriptome analysis under antagonistic conditions revealed significant downregulation of Cd toxicity-related genes and identified Y22D7AL.16, which has a C2H2-type zinc finger domain, as a novel gene involved in metal stress response, implying an alternative Cd-resilience mechanism. The expression profile of this gene shows that it plays a larger role in both development and metal stress adaption. These findings highlight the complexities of compound pollutant interactions, emphasizing the importance of including such dynamics in environmental risk assessments and control techniques.

A novel C2H2-type zinc-finger transcription factor, CitZAT4, regulates ethylene-induced orange coloration in Satsuma mandarin flavedo (Citrus unshiu Marc.).

Ethylene treatment promotes orange coloration in the flavedo of Satsuma mandarin (Citrus unshiu Marc.) fruit, but the corresponding regulatory mechanism is still largely unknown. In this study, we identified a C2H2-type zinc-finger transcription factor, CitZAT4, the expression of which was markedly induced by ethylene. CitZAT4 directly binds to the CitPSY promoter and activates its expression, thereby promoting carotenoid biosynthesis. Transient expression in Satsuma mandarin fruit and stable transformation of citrus calli showed that overexpressing of CitZAT4 inhibited CitLCYE expression, thus inhibiting α-branch yellow carotenoid (lutein) biosynthesis. CitZAT4 overexpression also enhanced the transcript levels of CitLCYB, CitHYD, and CitNCED2, promoting β-branch orange carotenoid accumulation. Molecular biochemical assays, including yeast one-hybrid (Y1H), electrophoretic mobility shift (EMSA), chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR), and luciferase (LUC) assays, demonstrated that CitZAT4 directly binds to the promoters of its target genes and regulates their expression. An ethylene response factor, CitERF061, which is induced by ethylene signaling, was found to directly bound to the CitZAT4 promoter and induced its expression, thus positively regulating CitZAT4-mediated orange coloration in citrus fruit. Together, our findings reveal that a CitZAT4-mediated transcriptional cascade is driven by ethylene via CitERF061, linking ethylene signaling to carotenoid metabolism in promoting orange coloration in the flavedo of Satsuma mandarin fruit. The molecular regulatory mechanism revealed here represents a significant step toward developing strategies for improving the quality and economic efficiency of citrus crops.

SUPERMAN Targets PHRAGMOPLAST ORIENTING KINESIN to Negatively Regulate Leaf Cell Division in Poplar.

Plant organs achieve their specific size and shape through the coordination of cell division and cell expansion, processes that are profoundly influenced by environmental cues. Cytokinesis during cell division depends on the position of the cytokinetic wall, but how this process responses to environment fluctuations remains underexplored. Here, we investigated a regulatory module involving C2H2-type zinc finger protein (C2H2-ZFP) in leaf morphology during drought stress. A total of 123 C2H2-ZFP members were identified through a comparative genome survey in Populus alba × P. glandulosa '84K'. Among them, PagSUPa, an orthologous gene of Arabidopsis SUPERMAN, was selected due to its responsiveness to drought stress and was further confirmed to play a role in leaf development. Phenotypic characterization and cellular analysis revealed that PagSUPa fine-tunes the duration of cell proliferation in the adaxial epidermis, thereby influencing leaf morphology by modulating leaf adaxial-abaxial polarity. Additionally, we found that PagSUPa directly suppresses the expression of PHRAGMOPLAST ORIENTING KINESIN1 (PagPOK1) and PagPOK2, genes encoding proteins involved in phragmoplast orientation and position, which results in impaired cytokinesis and cell wall organization. This study provides novel insights into the regulatory network governed by the SUP gene during leaf development, specifically in relation to cell division.

Antisense transcription from stress-responsive transcription factors fine-tunes the cold response in Arabidopsis.

Transcription of antisense long noncoding RNAs (lncRNAs) occurs pervasively across eukaryotic genomes. Only a few antisense lncRNAs have been characterized and shown to control biological processes, albeit with idiosyncratic regulatory mechanisms. Thus, we largely lack knowledge about the general role of antisense transcription in eukaryotic organisms. Here, we characterized genes with antisense transcription initiating close to the poly(A) signal of genes (PAS genes) in Arabidopsis (Arabidopsis thaliana). We compared plant native elongation transcript sequencing (plaNET-seq) with RNA sequencing during short-term cold exposure and detected massive differences between the response in active transcription and steady-state levels of PAS gene-derived mRNAs. The cold-induced expression of transcription factors B-BOX DOMAIN PROTEIN28 (BBX28) and C2H2-TYPE ZINC FINGER FAMILY PROTEIN5 (ZAT5) was detected by plaNET-seq, while their steady-state level was only slightly altered due to high mRNA turnover. Knockdown of BBX28 and ZAT5 or of their respective antisense transcripts severely compromised plant freezing tolerance. Decreased antisense transcript expression levels resulted in a reduced cold response of BBX28 and ZAT5, revealing a positive regulatory role of both antisense transcripts. This study expands the known repertoire of noncoding transcripts. It highlights that native transcription approaches can complement steady-state RNA techniques to identify biologically relevant players in stress responses.

C2H2-type zinc-finger protein BCL11B suppresses avian Leukosis virus subgroup J replication by regulating apoptosis

Apoptosis plays a crucial role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J), an avian oncogenic retrovirus, has been shown to suppress apoptosis while promoting its own replication. ALV-J induces myeloid tumors and hemangiomas in chickens resulting in significant economic losses for commercial layer and meat-type chicken production. B-cell lymphoma/leukemia 11B (Bcl11b) encodes a C2H2-type zinc finger protein—BCL11B, that exerts critical functions in cell proliferation, differentiation, and plays an essential role in the immune system. Previous study has been shown that Bcl11b is associated with ALV-J infection. In this study, we further investigated the pathological changes in ALV-J infected cells and examined the role and expression regulation of chicken Bcl11b. Our results demonstrate that Bcl11b, as an interferon-stimulated gene (ISG), encodes C2H2-type zinc finger protein BCL11B that promotes apoptosis to inhibit ALV-J infection. Additionally, gga-miR-1612 and gga-miR-6701-3p regulate apoptosis and are involved in ALV-J infection by targeting Bcl11b, thus revealing immune response strategies between the host and ALV-J. Although the underlying mechanisms require further validation, Bcl11b and its regulatory miRNAs are the first to demonstrate inhibition of ALV-J replication via apoptosis. BCL11B can a valuable target for treating diseases triggered by ALV-J infection.

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes

BackgroundSETDB1 (SET domain bifurcated-1) is a histone H3-lysine 9 (H3K9)-specific methyltransferase that mediates heterochromatin formation and repression of target genes. Despite the assumed functional link between DNA methylation and SETDB1-mediated H3K9 trimethylations, several studies have shown that SETDB1 operates autonomously of DNA methylation in a region- and cell-specific manner. This study analyzes SETDB1-null HAP1 cells through a linked methylome and transcriptome analysis, intending to explore genes controlled by SETDB1-involved DNA methylation.Methods and resultsWe investigated SETDB1-mediated regulation of DNA methylation and gene transcription in human HAP1 cells using reduced-representation bisulfite sequencing (RRBS) and RNA sequencing. While two-thirds of differentially methylated CpGs (DMCs) in genic regions were hypomethylated in SETDB1-null cells, we detected a plethora of C2H2-type zinc-finger protein genes (C2H2-ZFP, 223 of 749) among the DMC-associated genes. Most C2H2-ZFPs with DMCs in their promoters were found hypomethylated in SETDB1-KO cells, while other non-ZFP genes with promoter DMCs were not. These C2H2-ZFPs with DMCs in their promoters were significantly upregulated in SETDB1-KO cells. Similarly, C2H2-ZFP genes were upregulated in SETDB1-null 293T cells, suggesting that SETDB1’s function in ZFP gene repression is widespread. There are several C2H2-ZFP gene clusters on chromosome 19, which were selectively hypomethylated in SETDB1-KO cells.ConclusionsSETDB1 collectively and specifically represses a substantial fraction of the C2H2-ZFP gene family. Through the en-bloc silencing of a set of ZFP genes, SETDB1 may help establish a panel of ZFP proteins that are expressed cell-type specifically and thereby can serve as signature proteins for cellular identity.

Hydrogen peroxide positively regulates ABA signaling via oxidative modification of the C2H2-type zinc finger protein ZFP36 in rice

The rice zinc finger protein ZFP36 serves as a pivotal regulator of the hydrogen peroxide (H2O2) signaling pathway in response to abscisic acid (ABA). Its role is crucial for integrating H2O2 signals with the plant defense mechanisms against water deficit and oxidative stress. However, it remains unclear whether ZFP36 directly modulates ABA-induced H2O2 signaling. This study explored the effects of oxidative post-translational modifications (OxiPTMs) on ZFP36 in rice, with an emphasis on the H2O2-induced oxidation through its cysteine (Cys) residues. We found that ZFP36 undergoes oxidative modification as a target of H2O2 in the presence of ABA, specifically at Cys32. Employing quantitative detection and fluorescence assays, we observed that ZFP36 oxidation enhances the expression and activity of genes encoding protective antioxidant enzymes. Moreover, our investigation into the thioredoxin (Trx) and glutaredoxin (Grx) families revealed that OsTrxh1 facilitates the reduction of oxidized ZFP36. Genetic evidence indicates that ZFP36 positively influences rice resilience to oxidative and water stress, while OsTrxh1 exerts an opposing effect. These insights reveal a distinctive pathway for plant cells to perceive ABA-induced H2O2 signaling, advance our comprehension of H2O2 signaling dynamics, and ABA-related plant responses, and lay a vital groundwork for enhancing crop stress tolerance.

C2H2 proteins: Evolutionary aspects of domain architecture and diversification.

The largest group of transcription factors in higher eukaryotes are C2H2 proteins, which contain C2H2-type zinc finger domains that specifically bind to DNA. Few well-studied C2H2 proteins, however, demonstrate their key role in the control of gene expression and chromosome architecture. Here we review the features of the domain architecture of C2H2 proteins and the likely origin of C2H2 zinc fingers. A comprehensive investigation of proteomes for the presence of proteins with multiple clustered C2H2 domains has revealed a key difference between groups of organisms. Unlike plants, transcription factors in metazoans contain clusters of C2H2 domains typically separated by a linker with the TGEKP consensus sequence. The average size of C2H2 clusters varies substantially, even between genomes of higher metazoans, and with a tendency to increase in combination with SCAN, and especially KRAB domains, reflecting the increasing complexity of gene regulatory networks.