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PubMed2025

Analog epigenetic memory revealed by targeted chromatin editing.

Cells store information by means of chromatin modifications that persist through cell divisions and can hold gene expression silenced over generations. However, how these modifications may maintain other gene expression states has remained unclear. This study shows that chromatin modifications can maintain a wide range of gene expression levels over time, thus uncovering analog epigenetic memory. By engineering a genomic reporter and epigenetic effectors, we tracked the gene expression dynamics following targeted perturbations to the chromatin state. We found that distinct grades of DNA methylation led to corresponding, persistent gene expression levels. Altering the DNA methylation grade, in turn, resulted in permanent loss of gene expression memory. Consistent with experiments, our chromatin modification model indicates that analog memory arises when the positive feedback between DNA methylation and repressive histone modifications is lacking. This discovery will lead to a deeper understanding of epigenetic memory and to new tools for synthetic biology.

Epigenesis, Genetic↗
PubMed1977

Cytotoxic T lymphocytes specific for I region determinants do not require interactions with H-2K or D gene products.

Gene products coded for by the major hisocompatibility complex (MHC) can serve as target antigens for cytotoxic T lymphocytes (CTL) (1). A variety of test systems are available which have yielded information consistently reinforcing the importance of this complex of genes in the generation and effector phases of the cytotoxic immune response. Originally, it was shown that allogeneically-induced CTL had specificity primarily for the products of the K and D loci of the mouse H-2 complex (2). More recently this has also been found to be the case for xenogeneic immunizations (3,4). Additional examples of T cell-mediated lysis have been reported involving viral-infected or chemically- modified syngeneic stimulating and target cells in which homology at H-2K or H-2D was required between the responding and target cells for appreciable lysis to occur (5-7). Moreover, CTL specific for minor histocompatability antigens are able to lyse only target cells bearing these membrane antigens and sharing a common H-2K or H2-D gene product with the effector (8,9). Two hypotheses have been proposed to explain the requirement for H-2 identity between effector and targets in these systems. CTL may recognize new antigenic determinants created by the interaction of the modifier with syngeneic K and D gene products. Alternately, a dual recognition system my exist, requiring an antigen-specific receptor as well as a second receptor with specificity for homologous H-2K or H-2D determinants (5). Neither model can be excluded at this time. The I region also contains genes coding for histocompatibility loci since animals differing at the I-A or I-C regions of the H-2 complex reject skin grafts (10-12), though less rapidly than mice differing at the H-2K or H-2D regions, Also CTL can be generated to I region determinants but less efficiently than CTL specific for H-2K or H-2D gene products (12-14). The question can therefore be raised, whether the I region minor histocompatibility loci function independently from the H-2K or H-2D loci or whether I region-specific cytolysis requires the participation of H-2K or H-2D gene products of the target cell. This communication illustrates the generation of CTL showing specificity for I region determinants in primary mixed lymphocyte cultures. Further, we demonstrate by genetic analysis and byt eh use of speficit alloantisera that CTL directed to Ia determinants (a) do not see these antigens as modifications of H-2K or H-2D gene products but as independent gene products coded for by the I region, and (b) they do not require interaction with target cells bearing the same H-2K or H-2D gene product as the effect CTL.

Animals↗
PubMed1978

Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein.

Avian sarcoma virus (ASV) induces sarcomas in animals and transforms fibroblasts to a neoplastic state in cell culture. A single viral gene (src) is responsible for both the induction and maintenance of neoplastic transformation. Recent work has identified a protein with a molecular weight of 60,000 daltons that is apparently encoded in src and may be the effector molecule for the gene (Brugge and Erikson, 1977; Purchio et al, 1978). The putative product of src can be immunoprecipitated by antisera obtained from rabbits bearing tumors induced by ASV. We have used this approach to isolate the protein to characterize further its genetic origins and possible function. Our rabbit tumor antisera precipitated a protein with a molecular weight of 60,000 daltons; according to serological, biochemical and genetic criteria, this protein is encoded in src. We found that this protein is phosphorylated and therefore denoted it pp60. Phosphorylation of pp60 could be accomplished in vitro with extracts of ASV-infected cells. A temperature-sensitive conditional mutation in src had no demonstrable effect on either the production or stability of pp60 in the infected cell, but phosphorylation of the protein was temperature-sensitive. Since the mutant src is not expressed at the restrictive temperature, our findings raise the possibility that phosphorylation of pp60 is required for its function as the putative effector of src. Immunoprecipitates prepared with extracts of ASV-infected cells and the rabbit tumor antisera contained a protein kinase activity that catalyzed phosphorylation of the heavy chains of immunoglobulin molecules, using either ATP or GTP as phosphate donor. The kinase activity immunoprecipitated in parallel with pp60 was obtained only from cells that contained a functioning product of src and could not be precipitated with antisera directed against structural proteins of ASV. A temperature-sensitive conditional mutation in src caused the kinase activity to be thermally inactivated in vitro far more rapidly than the activity from cells infected with wild-type virus. We conclude that both the protein kinase and pp60 are encoded in src, and that the enzymatic activity may be an intrinsic property of pp60. Phosphorylation of pp60 in cellular extracts was inhibited by calcium ion, whereas the immunoprecipitable kinase activity was not, suggesting that the kinase responsible for pp60 phosphorylation may be distinct from that encoded in src. Collett and Erikson (1978) have also identified a protein kinase activity associated with pp60. These findings raise the possibility that phosphorylation of specific cellular targets might account for transformation of the host cell by src.

Adenosine Triphosphate↗
PubMed2023

Evolution and assembly of Anopheles aquasalis's immune genes: primary malaria vector of coastal Central and South America and the Caribbean Islands.

Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various Anopheles species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the Anopheles aquasalis genome, it was possible to obtain more information about the evolution of the immune response genes. Anopheles aquasalis has 278 immune genes in 24 families or groups. Comparatively, the American anophelines possess fewer genes than Anopheles gambiae s. s., the most dangerous African vector. The most remarkable differences were found in the pathogen recognition and modulation families like FREPs, CLIP and C-type lectins. Even so, genes related to the modulation of the expression of effectors in response to pathogens and gene families that control the production of reactive oxygen species were more conserved. Overall, the results show a variable pattern of evolution in the immune response genes in the anopheline species. Environmental factors, such as exposure to different pathogens and differences in the microbiota composition, could shape the expression of this group of genes. The results presented here will contribute to a better knowledge of the Neotropical vector and open opportunities for malaria control in the endemic-affected areas of the New World.

Animals↗
PubMed1975

The effect of gene concentration and relative gene dosage on gene output in Escherichia coli.

The differential rate of synthesis of several Escherichia coli gene products was measured under conditions in which the average number of copies of the corresponding chromosomal gene had been changed by altering the replication velocity of the chromosome. The data show that in steady state exponential cultures the output of genes in a fully repressed, fully derepressed, or non-repressible state is proportional to the average number of copies of the gene per unit mass (gene: mass ratio) and does not depend on the number of copies of the gene relative to all other genes (gene: DNA ratio). In contrast, the output of a gene which was under regulation by endogenously generated effectors was independent of such changes in gene frequency. The relationship found between the number of copies of a gene per unit of cell mass and enzyme output provides a new method for determining the location of the chromosome origin and the direction of replication in bacteria.

Alleles↗
PubMed2025

Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network.

TP53, the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite the importance of p53 in tumor suppression, the specific p53 target genes important for tumor suppression remain unclear. Recent studies have identified the p53-inducible gene Zmat3 as a critical effector of tumor suppression, but many questions remain regarding its p53-dependence, activity across contexts, and mechanism of tumor suppression alone and in cooperation with other p53-inducible genes. To address these questions, we used Tuba-seqUltra somatic genome editing and tumor barcoding in a mouse lung adenocarcinoma model, combinatorial in vivo CRISPR/Cas9 screens, meta-analyses of gene expression and Cancer Dependency Map data, and integrative RNA-sequencing and shotgun proteomic analyses. We established Zmat3 as a core component of p53-mediated tumor suppression and identified Cdkn1a as the most potent cooperating p53-induced gene in tumor suppression. We discovered that ZMAT3/CDKN1A serve as near-universal effectors of p53-mediated tumor suppression that regulate cell division, migration, and extracellular matrix organization. Accordingly, combined Zmat3-Cdkn1a inactivation dramatically enhanced cell proliferation and migration compared to controls, akin to p53 inactivation. Together, our findings place ZMAT3 and CDKN1A as hubs of a p53-induced gene program that opposes tumorigenesis across various cellular and genetic contexts.

Animals↗
PubMed2026

Deletion of the Salmonella pathogenicity island 2 gene, spiC, in attenuated Salmonella Typhimurium VNP20009 optimizes its potential for bacterial schwannoma therapy.

UNLABELLED: Recent advances in systems biology and immunotherapy have spurred the investigation of bacteria as therapeutic vehicles for cancer treatment. Currently, Bacillus Calmette-Guérin remains the only FDA-approved bacterial cancer therapy; it is a live attenuated mycobacterium that is indicated for the treatment and prophylaxis of carcinoma in situ of the urinary bladder and for the prophylaxis of primary or recurrent papillary tumors following transurethral resection. Although safety concerns have been raised, attenuated Salmonella Typhimurium strains such as VNP20009 have advanced to clinical trials targeting fast-growing human tumors. Notably, this strain induces robust immunological control of slow-growing tumors such as NF2-related schwannomatosis (NF2-SWN) in preclinical murine models. Here, we genetically characterize VNP20009 with the goal of constructing genetically defined attenuated strains that retain its promising therapeutic features while improving safety. Specifically, we investigated the contribution of the Salmonella pathogenicity island I (SPI-1) and SPI-2 type III secretion systems to antitumor efficacy and biosafety. Mutation of the SPI-1 gene sipB, a key structural component required for SPI-1 type III secretion system function, partially reduced tumor control in NF2-SWN murine schwannoma models, suggesting that bacterial invasion alone does not fully account for antitumor activity. In contrast, deletion of the SPI-2 gene spiC, a key effector required for intracellular survival, preserved robust tumor regression in NF2-SWN murine schwannoma models while improving safety and reducing systemic toxicity. To create a genetically defined and tractable platform, we generated two attenuated strains-AST101 and AST101-ΔspiC-which retain key mutations present in VNP20009 but lack ill-characterized background mutations. In the syngeneic NF2-SWN mouse schwannoma model, both strains significantly suppressed tumor growth compared to PBS. Collectively, these findings support the development of rationally engineered Salmonella Typhimurium strains with enhanced safety and preserved antitumor efficacy. IMPORTANCE: Given long-standing safety concerns surrounding the therapeutic use of live bacteria, we constructed a ΔspiC mutant of VNP20009 and demonstrated that it provides a markedly improved safety profile while retaining antitumor efficacy in NF2-related schwannomatosis mouse schwannoma models. In addition, we created two genetically defined Salmonella Typhimurium strains, AST01 and AST01-ΔspiC, which incorporate the key-targeted mutations found in VNP20009 and VNP20009-ΔspiC, respectively. These engineered strains offer a well-defined genetic background, enabling precise investigation of the bacterial traits responsible for Salmonella Typhimurium-mediated tumor control and thus further improvement of attenuated strains optimized for bacteriotherapy of neoplasms.

Salmonella typhimurium↗
PubMed2026

Metagenomic polymorphic toxin effector and immunity profiling predicts microbiome development and disease-related dysbiosis.

Bacteria use antagonistic interbacterial weapons, such as polymorphic toxin secretion systems (TSS), to compete for niches in the human gut microbiome. We hypothesized that TSS influence gut microbiome development and disease-related dysbiosis. We developed a bioinformatic marker gene approach (PolyProf) to quantify TSS including ~200 effector and immunity genes and applied it to ~15,000 publicly available human metagenomes. PolyProf alpha and beta diversity readily distinguished 12 different human disease states and enabled the construction of highly accurate linear regression classifier machine learning models. Elastic net machine learning models integrating bacterial taxonomy with PolyProf had strong predictive value for 12 disease states, outperforming models utilizing taxonomy alone. During microbiome development in the first year of life, PolyProf alpha diversity increases, and beta diversity becomes increasingly like the maternal microbiome, influenced by vertical transfer, delivery mode, and breastfeeding. PolyProf is related to strain sharing among adults through social interactions. In summary, TSS genes strongly correlate with microbiome development and interpersonal strain sharing, suggesting roles for interbacterial antagonism. Since PolyProf distinguishes diverse adult disease statuses, these dynamics may contribute to non-genetic inheritance.IMPORTANCEPrevious research has demonstrated that bacteria compete within the gut microbiome using toxin secretion systems (TSS). How TSS contribute to human microbiome development and the microbiome alterations observed in human diseases is not known. This study develops a new bioinformatic tool for profiling TSS-related genes in metagenomic data. Application of this approach to large-scale human fecal metagenomic data demonstrates the dynamic association of TSS during microbiome development, including the exchange of strains among social contacts. TSS gene abundance patterns are highly predictive of 12 disease states. This study advances the field by enabling TSS profiling in metagenomes and by identifying disease and microbiome development biomarkers that provide hypotheses for future mechanistic studies and may be useful for disease diagnosis.

Dysbiosis↗
PubMed2025

Genome-Wide Aggregated Trans Effects Analysis Identifies Genes Encoding Immune Checkpoints as Core Genes for Rheumatoid Arthritis.

OBJECTIVE: The sparse effector "omnigenic" hypothesis postulates that the polygenic effects of common single nucleotide polymorphisms (SNPs) on a typical complex trait are mediated by trans effects that coalesce on expression of a relatively sparse set of core genes. The objective of this study was to identify core genes for rheumatoid arthritis by testing for association of rheumatoid arthritis with genome-wide aggregated trans effects (GATE) scores for expression of each gene as transcript in whole blood or as circulating protein levels. METHODS: GATE scores were calculated for 5,400 cases and 453,705 non-cases of primary rheumatoid arthritis in UK Biobank participants of European ancestry. RESULTS: Testing for association with GATE scores identified 16 putative core genes for rheumatoid arthritis outside the HLA region, of which six-TP53BP1, PDCD1, TNFRSF14, LAIR1, LILRA4, and IDO1-were supported by Mendelian randomization analysis based on the marginal likelihood of the causal effect parameter. Five of these 16 genes were validated by a reported association of rheumatoid arthritis with SNPs within 200 kb of the transcription site, eight by association of the measured protein level with rheumatoid arthritis in UK Biobank, 10 by experimental perturbation in mouse models of inflammatory arthritis, and two-CTLA4 and PDCD1-by evidence that drugs targeting the gene cause or ameliorate inflammatory arthritis in humans. Fourteen of these 16 genes are in pathways affecting immunity or inflammation, and six-CD5, CTLA4, TIGIT, LAIR1, TNFRSF14, and PDCD1-encode receptors that have been characterized as immune checkpoints exploited by cancer cells to escape the immune response. CONCLUSION: These results highlight the key role of immune checkpoints in rheumatoid arthritis and identify possible therapeutic targets.

Humans↗
PubMed2026

Precision Engineering of Evolution-Resilient Rice against Bacterial Blight.

The persistent conflict between rice and Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight, exemplifies a dynamic genetic arms race in agriculture. The cyclical deployment and erosion of major resistance (R) genes highlight the high adaptive potential of Xoo and the need for strategies that are durable rather than absolute. This review synthesizes a paradigm shift from reactive, single R-gene deployment toward proactive engineering of evolution-resilient resistance. We explore the molecular-genetic basis of Xoo adaptability, including TAL effector diversification, non-TAL virulence functions, genome variation, and immune suppression mechanisms. In response, we propose a framework for durable disease management with three connected components: precision disarmament through editing of susceptibility-gene effector-binding elements and executor/decoy designs; smart induction through targeted delivery and immune priming; and ecological fortification through protective microbiomes. We also discuss the limits, trade-offs, and field-validation requirements of these approaches. Integrating frontier technologies with evolutionary genetics, predictive genomics, and pathogen population dynamics can help develop rice varieties and deployment systems that are more difficult for Xoo populations to overcome.

CRISPR↗
PubMed1975

Incompatibility at irrelevant H-2 specificities augments in vivo stimulation of alloaggressive cells.

Lymphoid cells of mice were sensitized in vivo either by H-2 strain-specific tumor allografts or by activation in lethally irradiated F1 hybrids and tested for cytotoxicity on 51Cr-labeled target cells. The release of 51Cr varied linearly with the logarithm to the proportion of effector lymphocytes to target cells and with the time of interaction. The release of 51Cr was immunologically specific and restricted to H-2 incompatibility. Spleen cells immune to public specificities of the target genotype were not cytotoxic. However, lymphoid cells immune to only one private specificity of a third-party target genotype were highly cytotoxic. The cytotoxicity of activated thymus cells on target cells sharing one private specificity with the genotype used for sensitization was significantly enhanced when the effector thymocytes were activated also against H-2 specificities not shared by the target strain. The results suggest that gene products that facilitate sensitization of effector cells may be determined both by the H-2K and the H-2D end of the H-2 complex. It remains to be shown whether the products of these loci, operating during sensitization in vivo, are body-wide correlated to the lymphocyte-defined specificities detectable during the mixed leukocyte culture interaction.

Animals↗
PubMed2026

Genomes of the ex-type strains of Elsinoë mangiferae and E. perseae, the causal agents of scab on mango and avocado.

Elsinoë species are slow-growing, hemibiotrophic to necrotrophic fungi that cause scab diseases on economically important fruit crops. Genome resources for many host-specific species remain limited. We report high-quality draft genome assemblies for the ex-type strains of Elsinoë mangiferae (CBS 226.50) and E. perseae (CBS 406.34), causal agents of mango and avocado scab, respectively. Among 5 approaches tested, a Nanopore-only NextDenovo assembly produced the most contiguous genomes, yielding 24.5 Mb (E. mangiferae) and 25.1 Mb (E. perseae) assemblies with 13 and 18 contigs, respectively, BUSCO completeness scores of ∼94%, and multiple putative telomere-to-telomere chromosomes. Gene prediction identified 9,134 and 9,243 genes, respectively. Functional annotation revealed enrichment of metabolic and regulatory pathways, including those involved in posttranslational modification, protein transport, and secondary metabolism. Carbohydrate-active enzyme repertoires were small but conserved, consistent with stealth pathogenicity strategies and low plant cell wall degradation. Both genomes encoded large secretomes (>850 proteins), diverse protease repertoires (>300 proteins), Ecp2-like effector proteins, and multiple biosynthetic gene clusters, including clusters with similarity to those associated with elsinochrome and ACT-toxin II biosynthesis, some of which may contribute to host-pathogen interactions and disease development. A large fraction of genes lacked functional characterization, suggesting incomplete databases and/or the presence of lineage-specific genes potentially involved in virulence or host adaptation. These genome resources fill critical gaps for underrepresented Elsinoë species and provide taxonomically anchored references essential for diagnostics, comparative genomics, and research into the molecular basis of host specificity and pathogenicity in scab-causing fungi.

Persea↗
PubMed2026

Whole-genome characterization and phylogenetic placement of Fusarium oxysporum f. sp. vasinfectum isolates.

Fusarium wilt of cotton, caused by Fusarium oxysporum f. sp. vasinfectum (Fov), remains a persistent threat to cotton production worldwide. Among the known races, Fov race 4 and its extra-virulent variants cause particularly severe losses in Upland cotton. Although several Fov genome assemblies have been assigned to races, the genomic diversity and evolutionary relationships among pathogenic and non-pathogenic isolates associated with cotton outbreaks remain poorly understood at the whole-genome level. This study addressed these gaps by generating and comparing high-quality genome assemblies of four Fusarium isolates collected from Texas cotton fields: two pathogenic (TX17-24 and TX18-9) and two non-pathogenic (TX17-6 and TX18-6). Draft assemblies were generated using Oxford Nanopore long reads and polished with Illumina reads. Comparative genomic analyses showed that pathogenic isolates possessed larger genomes and more conserved orthologous families, whereas non-pathogenic isolates contained more unique genes. Analyses of predicted secreted effectors, transposable elements, and carbohydrate-active enzymes further distinguished pathogenic and non-pathogenic lineages, suggesting roles in virulence adaptation and genome plasticity. Phylogenomic analyses using k-mer-based, assembly- and alignment-free methods incorporated all available long-read Fov genomes and revealed substantial genetic diversity within races 1 and 4, clustering isolates into multiple sublineages. These findings show that Fov race diversification is underestimated when based on traditional classification schemes and may be shaped by host specialization, geographic separation, or horizontal gene transfer. This work advances our understanding of the genomic diversity and evolutionary dynamics of Fov and establishes a foundation for improved race identification and characterization of Fusarium wilt pathogenesis in cotton.

Fusarium oxysporum↗
PubMed2025

Mapping genetic and phenotypic diversity of Pseudomonas aeruginosa across clinical and environmental isolation sites.

Pseudomonas aeruginosa is a clinically significant opportunistic pathogen adept at thriving in both host-associated and environmental settings. To define the extent to which P. aeruginosa isolates specialize across niches and identify genotype-phenotype correlates, we performed whole genome sequencing and comprehensive phenotypic characterization of 125 P. aeruginosa isolates from diverse clinical and environmental sites, evaluating virulence-associated traits, including motility, cytotoxicity, biofilm formation, pyocyanin production, and antimicrobial susceptibility. We identify that genomic diversity does not correlate with isolation source or most virulence phenotypes. Instead, we find that the two major P. aeruginosa clades (Groups A and B) delineate phylogeny and cytotoxicity, with Group B strains showing significantly higher cytotoxicity than Group A. Sequence analysis revealed previously uncharacterized alleles of genes encoding type III secretion effector proteins. We observed high variability amongst strains and isolation sources in all four assayed virulence phenotypes. Antimicrobial resistance (AMR) is exclusively observed in clinical isolates, not environmental, reflecting antibiotic exposure-driven selection. Bacterial GWAS revealed a statistically significant association between cytotoxicity and exoU presence, and we identified a novel exoU allelic variant with decreased cytotoxicity, demonstrating that functional diversity within well-characterized virulence factors may still influence pathogenic outcomes. In summary, our analyses of 125 diverse isolates suggest that the ability of P. aeruginosa to thrive across diverse niches is driven by broadly conserved genetic repertoire rather than niche-specific accessory genes.

Journal Article↗
PubMed1975

Control of expression of the pyr genes in Salmonella typhimurium: effects of variations in uridine and cytidine nucleotide pools.

The differential rate of synthesis of five of the pyrimidine biosynthetic enzymes coded for by pyrB-F, and the endogenous concentrations of the individual pyrimidine nucleotides were determined in specially constructed mutants of Salmonella typhimurium. In the mutants employed the different pyrimidine nucleotide pools may be manipulated individually during exponential growth. The results obtained indicate the following. (i) The expression of pyrB, pyrE, and pyrF is controlled by a uridine nucleotide in a noncoordinate manner. (ii) The expression of pyrC and pyrD is regulated predominantly by a cytidine nucleotide. Under all conditions investigated, their expression seems to be coordinated, even though the genes are not contiguous on the chromosome. (iii) The low-molecular-weight effectors involved in controlling the expression of the pyr genes are neither uridine 5'-monophosphate nor cytidine 5'-monophosphate, but rather the corresponding di- or triphosphates.

Amidohydrolases↗
PubMed1975

Poliovirus temperature-sensitivie mutants defective in cytopathic effects are also defective in synthesis of double-stranded RNA.

The proportion of cells absorbing trypan blue (tb-+ character) can be used to measure the late c.p.e. of wild-type poliovirus (ts-+. tb-+), which was the same at restrictive (39-2 to 39-6 degrees C) or permissive (37 degrees C) temperatures. Of twenty ts mutants, seven showed normal c.p.e. at 37 degrees C but were defective in C.P.E. (TB) AT 39-5 degrees C; all seven tb mutants have previously been shown (Cooper et al. 1971) to give evidence of a primary defect in replicase 1 activity (to make the complementary or minus strand of virus RNA). The remainder (tb-+) have all previously been shown to give evidence of a primary defect either in replicase II activity (to make progeny plus strands) or in structural protein. Thus, the late c.p.e. is dependent on a product of the replicase I gene, of which the in vivo effector is probably double-stranded RNA. Late c.p.e. is not caused by prevention of host protein, RNA or DNA synthesis and is not necessarily correlated with lysosomal enzyme release. The tb mutants were also defective in inducing early changes in chromatin (chr) and in prevention of thymidine incorporation (pti), but the tb and pti/chr characters are probably independent expressions of replicase I activity. Virus growth does not depend on repression of DNA synthesis. Poliovirus represses the activities of host DNA-dependent RNA polymerase I and II to an equal extent. There is no evidence that repression of DNA or RNA synthesis results from direct interaction of virus protein with the DNA.

Acridines↗
PubMed1978

Innate cytotoxicity of CBA mouse spleen cells to Sendai virus-infected L cells.

The presence in the spleens of unsensitized CBA mice of cells that are spontaneously cytotoxic for Sendai virus-infected L cells was confirmed. This innate cytotoxic activity to virus-infected cells was shown to exhibit some H-2 restriction. Partial identity of only the D end of the H-2 gene complex between the target and effector cells was required to produce cytolysis. Attempts to characterize the kind of cell active in this system indicated that neither the theta antigen nor the surface immunoglobulin markers were present. Furthermore, the cells appeared to have no adherent or phagocytic properties. The relationship between the effector cells responsible for innate cytotoxicity to virus-infected cells and the natural killer (NK) cells spontaneously cytotoxic for certain tumor cells is discussed.

Animals↗
PubMed2025

dCas-Based Tools to Visualize Chromatin or Modify Epigenetic Marks at Specific Plant Genomic Loci.

Development of locus-specific approaches targeting precise regions on chromatin, for locus/transcription visualization or transcription/epigenetic marks editing, is a critical challenge in functional genetics and epigenetics. Systems engineered from the clustered regularly interspaced short palindromic repeats (CRISPR) and its associated endonuclease (Cas) operate through DNA sequence-specific recognition by so-called guide RNAs, which provides high flexibility and modularity for precise chromatin visualization or edition. Here, we provide an overview of the CRISPR/Cas-derived tools developed for visualization of chromatin loci in live imaging or for effective modification of gene expression. These tools make use of effector modules that combine activators, repressors, and epigenetic modifiers with a deactivated Cas protein (dCas). We present how their use in plants brought advances in visualizing or manipulating the expression of loci involved in agronomically interesting traits such as flowering time and response to drought or heat. We also discuss the limitations and future improvements of the dCas-related technologies, such as more compact and combinatorial systems, spatiotemporal targeting for fine-tuning of gene expression, and live visualization of chromatin dynamics.

Chromatin↗