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1.
Int J Mol Sci ; 25(8)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38673993

RESUMEN

Cucumber (Cucumis sativus L.) is a globally prevalent and extensively cultivated vegetable whose yield is significantly influenced by various abiotic stresses, including drought, heat, and salinity. Transcription factors, such as zinc finger-homeodomain proteins (ZHDs), a plant-specific subgroup of Homeobox, play a crucial regulatory role in stress resistance. In this study, we identified 13 CsZHDs distributed across all six cucumber chromosomes except chromosome 7. Phylogenetic analysis classified these genes into five clades (ZHDI-IV and MIF) with different gene structures but similar conserved motifs. Collinearity analysis revealed that members of clades ZHD III, IV, and MIF experienced amplification through segmental duplication events. Additionally, a closer evolutionary relationship was observed between the ZHDs in Cucumis sativus (C. sativus) and Arabidopsis thaliana (A. thaliana) compared to Oryza sativa (O. sativa). Quantitative real-time PCR (qRT-PCR) analysis demonstrated the general expression of CsZHD genes across all tissues, with notable expression in leaf and flower buds. Moreover, most of the CsZHDs, particularly CsZHD9-11, exhibited varying responses to drought, heat, and salt stresses. Virus-induced gene silencing (VIGS) experiments highlighted the potential functions of CsZHD9 and CsZHD10, suggesting their positive regulation of stomatal movement and responsiveness to drought stress. In summary, these findings provide a valuable resource for future analysis of potential mechanisms underlying CsZHD genes in response to stresses.


Asunto(s)
Cucumis sativus , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Cucumis sativus/genética , Cucumis sativus/metabolismo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Dedos de Zinc/genética , Sequías , Cromosomas de las Plantas/genética , Perfilación de la Expresión Génica
2.
BMC Genomics ; 25(1): 385, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641598

RESUMEN

BACKGROUND: The C2H2 zinc finger protein family plays important roles in plants. However, precisely how C2H2s function in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear. RESULTS: In this study, a total of 69 OpC2H2 zinc finger protein genes were identified and clustered into five Groups. Seven tandem and ten fragment repeats were found in OpC2H2s, which underwent robust purifying selection. Of the identified motifs, motif 1 was present in all OpC2H2s and conserved at important binding sites. Most OpC2H2s possessed few introns and exons that could rapidly activate and react when faced with stress. The OpC2H2 promoter sequences mainly contained diverse regulatory elements, such as ARE, ABRE, and LTR. Under salt stress, two up-regulated OpC2H2s (OpC2H2-1 and OpC2H2-14) genes and one down-regulated OpC2H2 gene (OpC2H2-7) might serve as key transcription factors through the ABA and JA signaling pathways to regulate the growth and development of Opisthopappus species. CONCLUSION: The above results not only help to understand the function of C2H2 gene family but also drive progress in genetic improvement for the salt tolerance of Opisthopappus species.


Asunto(s)
Dedos de Zinc CYS2-HIS2 , Dedos de Zinc CYS2-HIS2/genética , Estrés Salino/genética , Genoma de Planta , Factores de Transcripción/metabolismo , Dedos de Zinc/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia
3.
Proc Natl Acad Sci U S A ; 121(17): e2320938121, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38635637

RESUMEN

The MYC-Associated Zinc Finger Protein (MAZ) plays important roles in chromatin organization and gene transcription regulation. Dysregulated expression of MAZ causes diseases, such as glioblastoma, breast cancer, prostate cancer, and liposarcoma. Previously, it has been reported that MAZ controls the proinflammatory response in colitis and colon cancer via STAT3 signaling, suggesting that MAZ is involved in regulating immunity-related pathways. However, the molecular mechanism underlying this regulation remains elusive. Here, we investigate the regulatory effect of MAZ on interferon-gamma (IFN-γ)-stimulated genes via STAT1, a protein that plays an essential role in immune responses to viral, fungal, and mycobacterial pathogens. We demonstrate that about 80% of occupied STAT1-binding sites colocalize with occupied MAZ-binding sites in HAP1/K562 cells after IFN-γ stimulation. MAZ depletion significantly reduces STAT1 binding in the genome. By analyzing genome-wide gene expression profiles in the RNA-Seq data, we show that MAZ depletion significantly suppresses a subset of the immune response genes, which include the IFN-stimulated genes IRF8 and Absent in Melanoma 2. Furthermore, we find that MAZ controls expression of the immunity-related genes by changing the epigenetic landscape in chromatin. Our study reveals an important role for MAZ in regulating immune-related gene expression.


Asunto(s)
Cromatina , Interferón gamma , Masculino , Humanos , Interferón gamma/genética , Interferón gamma/farmacología , Cromatina/genética , Regulación de la Expresión Génica , Unión Proteica , Dedos de Zinc/genética , Factor de Transcripción STAT1/genética
4.
Biochim Biophys Acta Mol Cell Res ; 1871(4): 119707, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38493895

RESUMEN

Ribosomes across species contain subsets of zinc finger proteins that play structural roles by binding to rRNA. While the majority of these zinc fingers belong to the C2-C2 type, the large subunit protein L36 in bacteria and mitochondria exhibits an atypical C2-CH motif. To comprehend the contribution of each coordinating residue in S. cerevisiae bL36m to mitoribosome assembly and function, we engineered and characterized strains carrying single and double mutations in the zinc coordinating residues. Our findings reveal that although all four residues markedly influence protein stability, C to A mutations in C66 and/or C69 have a more pronounced effect compared to those at C82 and H88. Importantly, protein stability directly correlates with the assembly and function of the mitoribosome and the growth rate of yeast in respiratory conditions. Mass spectrometry analysis of large subunit particles indicates that strains deleted for bL36m or expressing mutant variants have defective assembly of the L7/L12 stalk base, limiting their functional competence. Furthermore, we employed a synthetic bL36m protein collection, including both wild-type and mutant proteins, to elucidate their ability to bind zinc. Our data indicate that mutations in C82 and, particularly, H88 allow for some zinc binding albeit inefficient or unstable, explaining the residual accumulation and activity in mitochondria of bL36m variants carrying mutations in these residues. In conclusion, stable zinc binding by bL36m is essential for optimal mitoribosome assembly and function. MS data are available via ProteomeXchange with identifierPXD046465.


Asunto(s)
Ribosomas Mitocondriales , Saccharomyces cerevisiae , Ribosomas Mitocondriales/química , Ribosomas Mitocondriales/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Dedos de Zinc/genética , Subunidades Ribosómicas Grandes/genética , Zinc/metabolismo
5.
Science ; 383(6688): eadk4422, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38484051

RESUMEN

Conditional protein degradation tags (degrons) are usually >100 amino acids long or are triggered by small molecules with substantial off-target effects, thwarting their use as specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glue complexes (MG-PACE) and evolved a 36-amino acid zinc finger (ZF) degron (SD40) that binds the ubiquitin ligase substrate receptor cereblon in complex with PT-179, an orthogonal thalidomide derivative. Endogenous proteins tagged in-frame with SD40 using prime editing are degraded by otherwise inert PT-179. Cryo-electron microscopy structures of SD40 in complex with ligand-bound cereblon revealed mechanistic insights into the molecular basis of SD40's activity and specificity. Our efforts establish a system for continuous evolution of molecular glue complexes and provide ZF tags that overcome shortcomings associated with existing degrons.


Asunto(s)
Degrones , Evolución Molecular Dirigida , Proteolisis , Ubiquitina-Proteína Ligasas , Dedos de Zinc , Microscopía por Crioelectrón , Talidomida/química , Ubiquitina-Proteína Ligasas/química , Ubiquitinación , Degrones/genética , Dedos de Zinc/genética , Quimera Dirigida a la Proteólisis , Evolución Molecular Dirigida/métodos , Humanos
6.
Microbiol Res ; 283: 127695, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38554651

RESUMEN

Cap expansion in agaricoid mushroom species is an important event for sexual reproduction because meiosis occurs in basidia under the cap, and basidiospores can be released by opening the cap. However, molecular mechanisms underlying cap expansion in basidiomycetes remain poorly understood. We aimed to elucidate the molecular mechanisms of cap expansion in basidiomycetes by analyzing the unique cap-expansionless UV mutant #13 (exp2-1) in Coprinopsis cinerea. Linkage analysis and consequent genome sequence analysis revealed that the gene responsible for the mutant phenotypes encodes a putative transcription factor with two C2H2 zinc finger motifs. The mutant that was genome-edited to lack exp2 exhibited an expansionless phenotype. Some of the genes encoding cell wall degradation-related enzymes showed decreased expression during cap expansion and autolysis in the exp2 UV and genome-edited mutant. The exp2 gene is widely conserved in Agaricomycetes, suggesting that Exp2 homologs regulate fruiting body maturation in Agaricomycetes, especially cap expansion in Agaricoid-type mushroom-forming fungi. Therefore, exp2 homologs could be a target for mushroom breeding to maintain shape after harvest for some cultivating mushrooms, presenting a promising avenue for further research in breeding techniques.


Asunto(s)
Agaricales , Basidiomycota , Cuerpos Fructíferos de los Hongos/genética , Agaricales/genética , Dedos de Zinc/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
7.
Gene ; 908: 148290, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38367853

RESUMEN

Viral diseases are crucial determinants affecting tobacco cultivation, leading to a substantial annual decrease in production. Previous studies have demonstrated the regulatory function of the C3HC4 family of plant zinc finger proteins in combating bacterial diseases. However, it remains to be clarified whether this protein family also plays a role in regulating resistance against plant viruses. In this study, the successful cloning of the zinc finger protein coding gene NbZFP1 from Nicotiana benthamiana has been achieved. The full-length coding sequence of NbZFP1 is 576 bp. Further examination and analysis of this gene revealed its functional properties. The induction of NbZFP1 transcription in N. benthamiana has been observed in response to TMV, CMV, and PVY. Transgenic N. benthamiana plants over-expressing NbZFP1 demonstrated a notable augmentation in the production of chlorophyll a (P < 0.05). Moreover, NbZFP1-overexpressing tobacco exhibited significant resistance to TMV, CMV, and PVY, as evidenced by a decrease in virus copies (P < 0.05). In addition, the defense enzymes activities of PAL, POD, and CAT experienced a significant increase (P < 0.05). The up-regulated expression of genes of NbPAL, NbNPR1 and NbPR-1a, which play a crucial role in SA mediated defense, indicated that the NbZFP1 holds promise in enhancing the virus resistance of tobacco plant. Importantly, the results demonstrate that NbZFP1 can be considered as a viable candidate gene for the cultivation of crops with enhanced virus resistance.


Asunto(s)
Infecciones por Citomegalovirus , Nicotiana , Nicotiana/genética , Clorofila A , Dedos de Zinc/genética , Antivirales , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Cancer Res ; 84(6): 808-826, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38345497

RESUMEN

Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe and inflammatory responses that promote immune rejection. KRAB domain-containing zinc finger proteins (KZFP) contribute to heterochromatin maintenance at transposable elements (TE). Here, we identified an association of upregulation of a cluster of primate-specific KZFPs with poor prognosis, increased copy-number alterations, and changes in the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL). Depleting two of these KZFPs targeting evolutionarily recent TEs, ZNF587 and ZNF417, impaired the proliferation of cells derived from DLBCL and several other tumor types. ZNF587 and ZNF417 depletion led to heterochromatin redistribution, replicative stress, and cGAS-STING-mediated induction of an interferon/inflammatory response, which enhanced susceptibility to macrophage-mediated phagocytosis and increased surface expression of HLA-I, together with presentation of a neoimmunopeptidome. Thus, cancer cells can exploit KZFPs to dampen TE-originating surveillance mechanisms, which likely facilitates clonal expansion, diversification, and immune evasion. SIGNIFICANCE: Upregulation of a cluster of primate-specific KRAB zinc finger proteins in cancer cells prevents replicative stress and inflammation by regulating heterochromatin maintenance, which could facilitate the development of improved biomarkers and treatments.


Asunto(s)
Heterocromatina , Neoplasias , Animales , Heterocromatina/genética , Dedos de Zinc/genética , Elementos Transponibles de ADN , Primates/genética , Inflamación/genética , Neoplasias/genética
9.
Nat Commun ; 15(1): 1045, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316778

RESUMEN

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.


Asunto(s)
Ciclina D1 , Proteínas de Unión al ADN , G-Cuádruplex , Factores de Transcripción , Humanos , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Dedos de Zinc/genética
10.
Gene ; 904: 148164, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38224923

RESUMEN

C2H2-type zinc finger proteins are one of the most widely studied families in plants and play important roles in abiotic stress responses. In the present study, the physicochemical properties, chromosomal locations, evolutionary relationships, and gene structures of 54 C2H2 zinc finger protein (ZFP) family members were analyzed in apple. The MdC2H2-ZFP genes were phylogenetically clustered into seven subfamilies distributed in different densities on 16 chromosomes. The RNA-seq data from various tissues revealed that MdC2H2-ZFPs differentially expressed among root, stem, leaf, flower, and fruits. Quantitative analysis of its expression characteristics showed that the MdC2H2-ZFP genes were rapidly induced as exposure to abiotic stresses such as drought, salt and low temperature etc. Under drought stress, the expression of eight members was significantly up-regulated, and the highest was obtained from MdC2H2-17; as exposure to salt stress, nine MdC2H2-ZFPs was obviously up-regulated, with the highest expression of MdC2H2-13; and under low temperature stress, the expression of seven members was highly up-regulated, and MdC2H2-13 also demonstrated the highest expression which is same as the case under salt stress. Therefore, some members of MdC2H2-ZFP gene family considerably involve in the multiple abiotic stress responses, which may better understand the function of this family and facilitate the breeding of apple for stress tolerance.


Asunto(s)
Dedos de Zinc CYS2-HIS2 , Malus , Dedos de Zinc CYS2-HIS2/genética , Malus/genética , Malus/metabolismo , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Fitomejoramiento , Estrés Fisiológico/genética , Filogenia , Dedos de Zinc/genética
11.
Transl Psychiatry ; 14(1): 59, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38272911

RESUMEN

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in rodent prefrontal cortex was previously demonstrated to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Following viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, inversion of ZFP189-mediated transcription in this brain area, achieved by viral delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. RNA sequencing of virally manipulated prefrontal cortex tissues reveals that ZFP189 transcription factors of opposing regulatory function (ZFP189WT versus ZFP189VPR) have opposite influence on the expression of genetic transposable elements as well as genes that participate in adaptive immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for complex social behaviors while regulating transposable element-rich regions of DNA and the expression of immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.


Asunto(s)
Elementos Transponibles de ADN , Factores de Transcripción , Ratones , Animales , Factores de Transcripción/genética , Corteza Prefrontal/metabolismo , Conducta Social , Dedos de Zinc/genética , Roedores/genética , Roedores/metabolismo , Inmunidad
12.
Insect Sci ; 31(2): 405-416, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37464965

RESUMEN

The Masculinizer gene, Masc, encodes a lepidopteran-specific novel CCCH-type zinc finger protein, which controls sex determination and dosage compensation in Bombyx mori. Considering the potential application of it in pest control, it is necessary to investigate the function of Masc gene in Hyphantria cunea, a globally invasive forest pest. In the present study, we identified and functionally characterized the Masc gene, HcMasc, in H. cunea. Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain, nuclear localization signal, and male determining domain, in which the last was confirmed to be required for its masculinization in BmN cell line. However, expression data showed that unlike male-biased expression in B. mori, HcMasc gene expresses in main all developmental stages or tissues in both sexes. Clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes. Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H. cunea and provide a foundation for developing better strategies to control this pest.


Asunto(s)
Bombyx , Mariposas Nocturnas , Femenino , Masculino , Animales , Diferenciación Sexual/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Bombyx/genética , Dedos de Zinc/genética
13.
Biochem Biophys Res Commun ; 694: 149399, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38134477

RESUMEN

Ikaros family proteins (Ikaros, Helios, Aiolos, Eos) are zinc finger transcription factors essential for the development and function of the adaptive immune system. They also control developmental events in neurons and other cell types, suggesting that they possess crucial functions across disparate cell types. These functions are likely shared among the organisms in which these factors exist, and it is thus important to obtain a view of their distribution and conservation across organisms. How this family evolved remains poorly understood. Here we mined protein, mRNA and DNA databases to identify proteins with DNA-binding domains homologous to that of Ikaros. We show that Ikaros-related proteins exist in organisms from all four deuterostome phyla (chordates, echinoderms, hemichordates, xenacoelomorpha), but not in more distant groups. While most non-vertebrates have a single family member, this family grew to six members in the acoel worm Hofstenia miamia, three in jawless and four in jawed vertebrates. Most residues involved in DNA contact from zinc fingers 2 to 4 were identical across the Ikaros family, suggesting conserved mechanisms for target sequence recognition. Further, we identified a novel KRKxxxPxK/R motif that inhibits DNA binding in vitro which was conserved across the deuterostome phyla. We also identified a EψψxxxψM(D/E)QAIxxAIxYLGA(D/E)xL motif conserved among human Ikaros, Aiolos, Helios and subsets of chordate proteins, and motifs that are specific to subsets of vertebrate family members. Some of these motifs are targets of mutations in human patients. Finally we show that the atypical family member Pegasus emerged only in vertebrates, which is consistent with its function in bone. Our data provide a novel evolutionary perspective for Ikaros family proteins and suggest that they have conserved regulatory functions across deuterostomes.


Asunto(s)
Factor de Transcripción Ikaros , Dedos de Zinc , Animales , Humanos , ADN , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/metabolismo , ARN Mensajero , Dedos de Zinc/genética
14.
Int J Mol Sci ; 24(23)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38069184

RESUMEN

The membrane-less organelles in cytoplasm that are presented as cytoplasmic foci were successively identified. Although multiple CCCH zinc-finger proteins have been found to be localized in cytoplasmic foci, the relationship between their specific localization and functions still needs further clarification. Here, we report that the heterologous expression of two Brassica campestris CCCH zinc-finger protein genes (BcMF30a and BcMF30c) in Arabidopsis thaliana can affect microgametogenesis by involving the formation of cytoplasmic foci. By monitoring the distribution of proteins and observing pollen phenotypes, we found that, when these two proteins were moderately expressed in pollen, they were mainly dispersed in the cytoplasm, and the pollen developed normally. However, high expression induced the assembly of cytoplasmic foci, leading to pollen abortion. These findings suggested that the continuous formation of BcMF30a/BcMF30c-associated cytoplasmic foci due to high expression was the inducement of male sterility. A co-localization analysis further showed that these two proteins can be recruited into two well-studied cytoplasmic foci, processing bodies (PBs), and stress granules (SGs), which were confirmed to function in mRNA metabolism. Together, our data suggested that BcMF30a and BcMF30c play component roles in the assembly of pollen cytoplasmic foci. Combined with our previous study on the homologous gene of BcMF30a/c in Arabidopsis, we concluded that the function of these homologous genes is conserved and that cytoplasmic foci containing BcMF30a/c may participate in the regulation of gene expression in pollen by regulating mRNA metabolism.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Brassica , Arabidopsis/genética , Arabidopsis/metabolismo , Brassica/genética , Brassica/metabolismo , Proteínas de Arabidopsis/genética , Polen/genética , Polen/metabolismo , ARN Mensajero/metabolismo , Zinc/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Dedos de Zinc/genética
15.
Genome Biol Evol ; 15(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37847041

RESUMEN

Krüppel-associated box (KRAB) zinc finger proteins (KZNFs) recognize and repress transposable elements (TEs); TEs are DNA elements that are capable of replicating themselves throughout our genomes with potentially harmful consequences. However, genes from this family of transcription factors have a much wider potential for genomic regulation. KZNFs have become integrated into gene-regulatory networks through the control of TEs that function as enhancers and gene promoters; some KZNFs also bind directly to gene promoters, suggesting an additional, more direct layer of KZNF co-option into gene-regulatory networks. Binding site analysis of ZNF519, ZNF441, and ZNF468 suggests the structural evolution of KZNFs to recognize TEs can result in coincidental binding to gene promoters independent of TE sequences. We show a higher rate of sequence turnover in gene promoter KZNF binding sites than neighboring regions, implying a selective pressure is being applied by the binding of a KZNF. Through CRISPR/Cas9 mediated genetic deletion of ZNF519, ZNF441, and ZNF468, we provide further evidence for genome-wide co-option of the KZNF-mediated gene-regulatory functions; KZNF knockout leads to changes in expression of KZNF-bound genes in neuronal lineages. Finally, we show that the opposite can be established upon KZNF overexpression, further strengthening the support for the role of KZNFs as bona-fide gene regulators. With no eminent role for ZNF519 in controlling its TE target, our study may provide a snapshot into the early stages of the completed co-option of a KZNF, showing the lasting, multilayered impact that retrovirus invasions and host response mechanisms can have upon the evolution of our genomes.


Asunto(s)
Primates , Dedos de Zinc , Animales , Dedos de Zinc/genética , Primates/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Elementos Transponibles de ADN , Redes Reguladoras de Genes
16.
Genes Cells ; 28(12): 831-844, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37778747

RESUMEN

Mouse ES cell populations contain a minor sub-population that expresses genes specifically expressed in 2-cell stage embryos. This sub-population consists of 2-cell-gene labeled cells (2CLCs) generated by the transient activation of the 2-cell specific genes initiated by the master regulator, Dux. However, the mechanism regulating the transient expression remains largely unclear. Here we reported a novel function of Zfp352, one of the 2-cell specific genes, in regulating the 2CLC sub-population. Zfp352 encodes zinc-finger transcription factor belonging to the Klf family. Dux transiently activates Zfp352 after the activation of Zscan4c in a subset of the 2CLC subpopulation. Interestingly, in the reporter assay, the transcriptional activation of Zscan4c by Dux is strongly repressed by the co-expression of Zfp352. However, the knockout of Zfp352 resulted in the repression of a subset of the 2-cell-specific genes. These data suggest the dual roles of Zfp352 in regulating the transient activation of the 2-cell-specific genes.


Asunto(s)
Proteínas de Unión al ADN , Células Madre Embrionarias de Ratones , Factores de Transcripción , Animales , Ratones , Regulación del Desarrollo de la Expresión Génica , Células Madre Embrionarias de Ratones/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Dedos de Zinc/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
17.
Int J Mol Sci ; 24(20)2023 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-37894862

RESUMEN

Q-type C2H2 zinc finger proteins (ZFPs), the largest family of transcription factors, have been extensively studied in plant genomes. However, the genes encoding this transcription factor family have not been explored in grapevine genomes. Therefore, in this study, we conducted a genome-wide identification of ZFP genes in three species of grapevine, namely Vitis vinifera, Vitis riparia, and Vitis amurensis, based on the sequence databases and phylogenetic and their conserved domains. We identified 52, 54, and 55 members of Q-type C2H2 ZFPs in V. vinifera, V. riparia, and V. amurensis, respectively. The physical and chemical properties of VvZFPs, VrZFPs, and VaZFPs were examined. The results showed that these proteins exhibited differences in the physical and chemical properties and that they all were hydrophobic proteins; the instability index showed that the four proteins were stable. The subcellular location of the ZFPs in the grapevine was predicted mainly in the nucleus. The phylogenetic tree analysis of the amino acid sequences of VvZFP, VaZFP, VrZFP, and AtZFP proteins showed that they were closely related and were divided into six subgroups. Chromosome mapping analysis showed that VvZFPs, VrZFPs, and VaZFPs were unevenly distributed on different chromosomes. The clustered gene analysis showed that the motif distribution was similar and the sequence of genes was highly conserved. Exon and intron structure analysis showed that 118 genes of ZFPs were intron deletion types, and the remaining genes had variable numbers of introns, ranging from 2 to 15. Cis-element analysis showed that the promoter of VvZFPs contained multiple cis-elements related to plant hormone response, stress resistance, and growth, among which the stress resistance elements were the predominant elements. Finally, the expression of VvZFP genes was determined using real-time quantitative PCR, which confirmed that the identified genes were involved in response to methyl jasmonate (MeJA), abscisic acid (ABA), salicylic acid (SA), and low-temperature (4 °C) stress. VvZFP10-GFP and VvZFP46-GFP fusion proteins were localized in the nucleus of tobacco cells, and VvZFP10 is the most responsive gene among all VvZFPs with the highest relative expression level to MeJA, ABA, SA and low-temperature (4 °C) stress. The present study provides a theoretical basis for exploring the mechanism of response to exogenous hormones and low-temperature tolerance in grapes and its molecular breeding in the future.


Asunto(s)
Dedos de Zinc CYS2-HIS2 , Dedos de Zinc CYS2-HIS2/genética , Filogenia , Proteínas de Plantas/metabolismo , Genoma de Planta , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Dedos de Zinc/genética
18.
BMC Genomics ; 24(1): 603, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821819

RESUMEN

Zinc finger-homeodomain (ZHD) proteins are mostly expressed in plants and are involved in proper growth and development and minimizing biotic and abiotic stress. A recent study identified and characterized the ZHD gene family in chilli (Capsicum annuum L.) to determine their probable molecular function. ZHD genes with various physicochemical characteristics were discovered on twelve chromosomes in chilli. We separated ZHD proteins into two major groups using sequence alignment and phylogenetic analysis. These groups differ in gene structure, motif distribution, and a conserved ZHD and micro-zinc finger ZF domain. The majority of the CaZHDs genes are preserved, early duplication occurred recently, and significant pure selection took place throughout evolution, according to evolutionary study. According to expression profiling, the genes were found to be equally expressed in tissues above the ground, contribute to plant growth and development and provide tolerance to biotic and abiotic stress. This in silico analysis, taken as a whole, hypothesized that these genes perform distinct roles in molecular and phytohormone signaling processes, which may serve as a foundation for subsequent research into the roles of these genes in other crops.


Asunto(s)
Capsicum , Capsicum/genética , Capsicum/metabolismo , Filogenia , Proteínas de Unión al ADN/genética , Dedos de Zinc/genética , Genes Homeobox , Estrés Fisiológico/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
19.
Front Biosci (Landmark Ed) ; 28(8): 162, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37664917

RESUMEN

BACKGROUND: Myc-associated zinc finger protein (MAZ) plays a role in cancer progression and metastasis. However, the role and underlying molecular mechanism of MAZ in thyroid cancer have not yet been fully elucidated. This study aimed to explore the clinical significance of MAZ in thyroid cancer tissues, and clarify its mechanism in the occurrence and development of thyroid cancer. METHODS: The expression level of MAZ protein in thyroid cancer tissues was detected by bioinformatics analysis and immunohistochemistry (IHC). The relationship between the expression level of MAZ and clinicopathological characteristics of thyroid cancer patients was analyzed by multivariate logistic regression analysis. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of MAZ in thyroid cancer cell lines. After MAZ knockdown cell lines were constructed, wound healing and Transwell assays were used to detect the migratory and invasive abilities of cancer cells. RESULTS: The results of IHC showed that the expression level of MAZ protein in thyroid cancer tissues was higher than that in normal adjacent thyroid tissues (p < 0.05), which was consistent with the high expression level of MAZ in thyroid cancer tissues found in The Cancer Genome Atlas (TCGA) database. The results of multivariate logistic regression analysis indicated that the expression level of MAZ was correlated with tumor diameter and tumor capsule of thyroid cancer patients. Moreover, patients with the high MAZ expression level had shorter overall and disease-free survival compared with thyroid cancer patients with the low MAZ expression level (p < 0.05). Further cell function assays indicated that downregulation of MAZ expression level could inhibit the migration and invasion of thyroid cancer cell lines. Moreover, the expression level of epithelial-mesenchymal transition (EMT)-related factor fibronectin 1 (FN1) was obtained from the RNA-seq of MAZ knockdown in thyroid cancer cells. RT-qPCR confirmed that the expression level of FN1 was elevated in MAZ knockdown cell lines (p < 0.05). Bioinformatics analysis indicated that the expression level of FN1 was upregulated in thyroid cancer tissues and had a negative relationship with the expression level of MAZ, as evidenced by correlation analysis. CONCLUSIONS: A high expression level of MAZ in thyroid cancer tissues was associated with a poor prognosis of patients. MAZ could affect the progression of thyroid cancer by inducing the EMT process.


Asunto(s)
Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Dedos de Zinc/genética
20.
Trends Plant Sci ; 28(12): 1347-1349, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37743166

RESUMEN

Sucrose non-fermenting kinase 1 (SnRK1) has emerged as a pivotal activator of the autophagy pathway; however, the reciprocal influence of autophagy on SnRK1 remains unknown. Yang et al. have recently revealed the existence of a feedback loop connecting autophagy and SnRK1 in terrestrial plants, involving the novel FCS-like zinc finger (FLZ) class of proteins.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Homeostasis/genética , Plantas/genética , Plantas/metabolismo , Dedos de Zinc/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo
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