Search Results (70)

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Bougainvillea spp. possesses vibrantly pigmented bracts that exhibit high ornamental value. Zinc finger proteins (ZFPs), one of the most extensive transcription factor families in plants, are implicated in diverse biological functions, including plant morphogenesis, transcriptional regulation, and responses to abiotic stress. Nevertheless, their regulatory roles in bract pigmentation in Bougainvillea remain unexplored. In the present investigation, 105 BbZFP genes were identified from the Bougainvillea genome via bioinformatic analyses and subsequently categorized into five subgroups according to the quantity and arrangement of their structural domains. Analysis of physicochemical characteristics demonstrated that the BbZFP family encompasses both acidic and basic proteins, all of which are hydrophilic and predominantly classified as unstable proteins. Gene structure analysis revealed that the majority of BbZFP genes comprise between one and five– introns. Cis-regulatory element analysis suggested that BbZFP promoter regions harbor multiple elements associated with abiotic stress responses, hormonal regulation, and light responsiveness, implying their possible participation in these physiological processes. Transcriptomic data analysis revealed distinct expression patterns of BbZFP genes among bracts of different colors. A quantitative real-time polymerase chain reaction (RT-qPCR) further confirmed that Bou_68928, Bou_1096, Bou_4400, and Bou_17631 were markedly upregulated in yellow bracts relative to white bracts, suggesting their involvement in flavonoid biosynthesis regulation. Meanwhile, Bou_1096 and Bou_17631 exhibited markedly elevated expression in red-purple bracts compared to white bracts, potentially regulating betacyanin biosynthesis in Bougainvillea. These findings offer candidate genes for molecular breeding strategies aimed at enhancing floral coloration in Bougainvillea. The next step will involve elucidating the functions of these genes in bract coloration. Full article

The possible regulatory effects of C2H2 zinc finger proteins, which are important transcription factors, on intertidal seaweed responses to abiotic stress are unclear. This study was conducted to comprehensively analyze the C2H2 gene family of a representative intertidal seaweed species (Pyropia haitanensis) and clarify its genomic characteristics and biological functions. A total of 107 PhC2H2 zinc finger protein-encoding genes distributed on five P. haitanensis chromosomes were identified and divided into three subgroups. The expression levels of 85, 61, 58, 45, and 41 PhC2H2 genes responded in the maturation of filaments, high-temperature, salt, low-irradiance, and dehydration stress, respectively. The PhC2H2 gene family was conserved during Porphyra evolution, with no indications of large-scale genome-wide replication events. On average, PhC2H2 genes had more transposable element (TE) insertions than Pyropia yezoensis and Porphyra umbilicalisC2H2 genes, suggesting that TE insertions may have been the main driver of PhC2H2 gene family expansion. A key gene (PhC2H2.94) screened following a quantitative trait locus analysis was significantly responsive to high-temperature stress and was associated with photosynthesis, peroxisomes, the ubiquitin proteasome pathway, and the endoplasmic reticulum-related protein processing pathway, which contribute to the stress tolerance of P. haitanensis. Additionally, PhC2H2.94 transgenic Chlamydomonas reinhardtii exhibited increased tolerance to heat stress. This study provides new insights and genetic resources for characterizing the molecular mechanism underlying intertidal seaweed responses to abiotic stresses and breeding stress-resistant macroalgae. Full article

Drought and soil salinization significantly constrain agricultural productivity, driving the need for molecular breeding strategies to enhance stress resistance. Zinc finger proteins play a critical role in plant response to abiotic stress. In this study, a gene encoding a C2H2-type zinc finger protein (AfZFP5) was cloned from Amorpha fruticosa, a species known for its strong adaptability. qRT-PCR analysis revealed that AfZFP5 expression is regulated by sorbitol, H₂O₂, NaCl, and NaHCO₃. And all four treatments can cause upregulation of AFZFP5 expression in the roots or leaves of Amorpha fruticosa within 48 h. Transgenic tobacco lines overexpressing AfZFP5 demonstrated enhanced tolerance to drought and salt–alkali stress at germination, seedling, and vegetative stages. Compared to wild-type plants, transgenic lines exhibited significantly higher germination rates, root lengths, and fresh weights when treated with sorbitol, NaCl, and NaHCO₃. Under natural drought and salt–alkali stress conditions, transgenic plants showed elevated activities of superoxide dismutase (SOD) and peroxidase (POD), and upregulated expression of oxidative stress-related kinase genes (NtSOD, NtPOD) during the vegetative stage. Additionally, transgenic tobacco displayed lower malondialdehyde (MDA) content and reduced staining levels with 3,3′diaminobenzidine (DAB) and Nitro blue tetrazolium (NBT), indicating enhanced reactive oxygen species (ROS) scavenging capacity by AfZFP5 upon salt–alkali stress. Under simulated drought with PEG6000 and salt–alkali stress, chlorophyll fluorescence intensity and Fv/Fm values in transgenic tobacco were significantly higher than in wild-type plants during the vegetative stage, suggesting that AfZFP5 mitigates stress-induced damage to the photosynthetic system. This study highlights the role of AfZFP5 in conferring drought and salt–alkali stress tolerance, providing genetic resources and a theoretical foundation for breeding stress-resistance crops. Full article

Background and Objectives: Zinc finger proteins are important transcription factors that regulate gene expression and play a critical role in neurodevelopment including autism spectrum disorders (ASDs). They are involved in a variety of cellular processes, including cell proliferation, differentiation, and apoptosis. Materials and Methods: Whole-exome sequencing (WES) analysis on a patient diagnosed with ASD. Results: Sequencing identified a homozygous insertion causing a stop codon, resulting in the removal of several functional domains including the zinc finger C2HC/C3H type of the ZC2HC1C protein. To date, no MIM entry has been assigned to the detected gene. In silico predictions described the variant as likely pathogenic, indicating an autosomal recessive inheritance pattern. In this study, we hypothesize that this homozygous mutation disrupts protein function and may represent a susceptibility gene for autism. The parents and the patient’s sister were healthy and carry the variant in the heterozygous condition. This gene is expressed in brain tissues showing high expression in both the choroid plexus (ChP) and midbrain, whose dysfunctions, as reported, may lead to ASD. Moreover, predictive pathway analyses indicated the probable involvement of this gene in primary cilia development. This process has been frequently linked to neurodevelopmental impairments, such as autism, as documented in previous studies. Conclusions: Further analyses are needed via in vitro functional assays or by ZC2HC1C gene knockout to validate its functional role. Full article

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. Full article

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. Full article

Salinity causes widespread crop loss and prompts plants to adapt through changes in gene expression. In this study, we aimed to investigate the function of the non-tandem CCCH zinc-finger (non-TZF) protein gene AtC3H3 in response to salt stress in Arabidopsis. AtC3H3, a gene from the non-TZF gene family known for its RNA-binding and RNase activities, was up-regulated under osmotic stress, such as high salt and drought. When overexpressed in Arabidopsis, AtC3H3 improved tolerance to salt stress, but not drought stress. The expression of well-known abscisic acid (ABA)-dependent salt stress-responsive genes, namely Responsive to Desiccation 29B (RD29B), RD22, and Responsive to ABA 18 (RAB18), and representative ABA-independent salt stress-responsive genes, namely Dehydration-Responsive Element Binding protein 2A (DREB2A) and DREB2B, was significantly higher in AtC3H3-overexpressing transgenic plants (AtC3H3 OXs) than in wild-type plants (WT) under NaCl treatment, indicating its significance in both ABA-dependent and -independent signal transduction pathways. mRNA-sequencing (mRNA-Seq) analysis using NaCl-treated WT and AtC3H3 OXs revealed no potential target mRNAs for the RNase function of AtC3H3, suggesting that the potential targets of AtC3H3 might be noncoding RNAs and not mRNAs. Through this study, we conclusively demonstrated that AtC3H3 plays a crucial role in salt stress tolerance by influencing the expression of salt stress-responsive genes. These findings offer new insights into plant stress response mechanisms and suggest potential strategies for improving crop resilience to salinity stress. Full article

Strawberry is frequently attacked by mites, which directly affects the yield and quality of this fruit species. The WRKY Group III transcription factors (TFs) play an important role in plant tolerance to biotic sources of stress, such as pathogens and insect pests. In this study, six Group III WRKY TFs (FaWRKY25, FaWRKY31, FaWRKY32, FaWRKY43, FaWRKY44, and FaWRKY45) were identified in strawberry. A phylogenetic analysis showed that the six WRKY III TFs were divided into two clades and all had a conserved WRKYGQK domain and the C-X₇-C-X₂₃-H-T-C zinc finger motif. An interaction network analysis revealed that FaWRKY44 was co-expressing with FaWRKY25 and FaWRKY45. The expression patterns showed that the WRKY Group III genes responded to plant hormones and mite infestation in strawberry. To further verify the role of FaWRKY25 in plant resistance to mites, we cloned the FaWRKY25 gene and overexpressed it in transgenic plants. An in vivo subcellular localization analysis indicated that the FaWRKY25 protein was localized in the nucleus. Fewer mites were also detected on the wild-type plants than on FaWRKY25-overexpressing transgenic plants, suggesting that FaWRKY25 negatively regulates the resistance of strawberry to mites. The present study advances our understanding on a potential target that mites use to manipulate host plant defenses. Full article

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. Full article

ZC4H2 encodes a C4H2-type zinc finger protein, mutations of which lead to a spectrum of diseases known as ZC4H2 associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear. Here, we showed that ZC4H2 is expressed in the developing bones in mice. ZC4H2 knockout mice were neonatal-lethal and smaller in size, with reduced calcification of long bones. Upon induced loss of ZC4H2 postnatally, the femoral bones developed an osteoporosis-like phenotype, with reduced bone mineral density, bone-volume fraction, and trabecular bone number. Knockdown of ZC4H2 showed no clear effect on the expression of osteogenic differentiation genes in in vitro models using mesenchymal stem cells. Interestingly, ZC4H2 knockdown significantly enhanced osteoclast differentiation and bone resorption in induced bone marrow-derived macrophages. We further confirmed that the number of osteoclasts in the long bone of ZC4H2 knockout mice was increased, as well as the expression of the serum bone resorption/osteoporosis marker CTX-1. Our study unveils a new role of ZC4H2 in osteoclast differentiation and bone development, providing new clues on the pathology of ZARD. Full article

Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in biotic and abiotic stress response. However, the members and expression patterns of C2H2 TFs in response to stresses in P. massoniana have not been performed. In this paper, 57 C2H2 zinc finger proteins of P. massoniana were identified and divided into five subgroups according to a phylogenetic analysis. In addition, six Q-type PmC2H2-ZFPs containing the plant-specific motif ‘QALGGH’ were selected for further study under different stresses. The findings demonstrated that PmC2H2-ZFPs exhibit responsiveness towards various abiotic stresses, including drought, NaCl, ABA, PEG, H₂O₂, etc., as well as biotic stress caused by the pine wood nematode. In addition, PmC2H2-4 and PmC2H2-20 were nuclear localization proteins, and PmC2H2-20 was a transcriptional activator. PmC2H2-20 was selected as a potential transcriptional regulator in response to various stresses in P. massoniana. These findings laid a foundation for further study on the role of PmC2H2-ZFPs in stress tolerance. Full article

A breakthrough “Green Revolution” in rice enhanced lodging resistance by using gibberellin-deficient semi-dwarf varieties. However, the gibberellic acid (GA) signaling regulation on rice disease resistance remains unclear. The resistance test showed that a positive GA signaling regulator DWARF1 mutant d1 was more susceptible while a negative GA signaling regulator Slender rice 1 (SLR1) mutant was less susceptible to sheath blight (ShB), one of the major rice diseases, suggesting that GA signaling positively regulates ShB resistance. To isolate the regulator, which simultaneously regulates rice lodging and ShB resistance, SLR1 interactors were isolated. Yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and Co-IP assay results indicate that SLR1 interacts with Calcineurin B-like-interacting protein kinase 31 (CIPK31). cipk31 mutants exhibited normal plant height, but CIPK31 OXs showed semi-dwarfism. In addition, the SLR1 level was much higher in CIPK31 OXs than in the wild-type, suggesting that CIPK31 OX might accumulate SLR1 to inhibit GA signaling and thus regulate its semi-dwarfism. Recently, we demonstrated that CIPK31 interacts and inhibits Catalase C (CatC) to accumulate ROS, which promotes rice disease resistance. Interestingly, CIPK31 interacts with Vascular Plant One Zinc Finger 2 (VOZ2) in the nucleus, and expression of CIPK31 accumulated VOZ2. Inoculation of Rhizoctonia solani AG1-IA revealed that the voz2 mutant was more susceptible to ShB. Thus, these data prove that CIPK31 promotes lodging and ShB resistance by regulating GA signaling and VOZ2 in rice. This study provides a valuable reference for rice ShB-resistant breeding. Full article

RAMOSA1 (RA1) is a Cys2-His2-type (C2H2) zinc finger transcription factor that controls plant meristem fate and identity and has played an important role in maize domestication. Despite its importance, the origin of RA1 is unknown, and the evolution in plants is only partially understood. In this paper, we present a well-resolved phylogeny based on 73 amino acid sequences from 48 embryophyte species. The recovered tree topology indicates that, during grass evolution, RA1 arose from two consecutive SUPERMAN duplications, resulting in three distinct grass sequence lineages: RA1-like A, RA1-like B, and RA1; however, most of these copies have unknown functions. Our findings indicate that RA1 and RA1-like play roles in the nucleus despite lacking a traditional nuclear localization signal. Here, we report that copies diversified their coding region and, with it, their protein structure, suggesting different patterns of DNA binding and protein–protein interaction. In addition, each of the retained copies diversified regulatory elements along their promoter regions, indicating differences in their upstream regulation. Taken together, the evidence indicates that the RA1 and RA1-like gene families in grasses underwent subfunctionalization and neofunctionalization enabled by gene duplication. Full article

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. Full article