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DNA N6-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in the human genome, and we cataloged 881,240 6mA sites accounting for â¼0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. DNA 6mA and N6-demethyladenine modification in the human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompanied by decreased N6AMT1 and increased ALKBH1 levels, and downregulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.
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Adenina/análogos & derivados , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Genoma Humano , DNA Metiltransferases Sítio Específica (Adenina-Específica)/metabolismo , Adenina/metabolismo , Homólogo AlkB 1 da Histona H2a Dioxigenase/genética , Animais , Carcinogênese/genética , DNA/genética , Metilação de DNA , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , DNA Metiltransferases Sítio Específica (Adenina-Específica)/genéticaRESUMO
Folate (vitamin B9) is important for plant root development, but the mechanism is largely unknown. Here we characterized a root defective mutant, folb2, in Arabidopsis, which has severe developmental defects in the primary root. The root apical meristem of the folb2 mutant is impaired, and adventitious roots are frequently found at the root-hypocotyl junction. Positional cloning revealed that a 61-bp deletion is present in the predicted junction region of the promoter and the 5' untranslated region of AtFolB2, a gene encoding a dihydroneopterin aldolase that functions in folate biosynthesis. This mutation leads to a significant reduction in the transcript level of AtFolB2. Liquid chromatography-mass spectrometry analysis showed that the contents of the selected folate compounds were decreased in folb2. Arabidopsis AtFolB2 knockdown lines phenocopy the folb2 mutant. On the other hand, the application of exogenous 5-formyltetrahydrofolic acid could rescue the root phenotype of folb2, indicating that the root phenotype is indeed related to the folate level. Further analysis revealed that folate could promote rootward auxin transport through auxin transporters and that folate may affect particular auxin/indole-3-acetic acid proteins and auxin response factors. Our findings provide new insights into the important role of folic acid in shaping root structure.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Raízes de Plantas/metabolismo , Meristema/genética , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas , MutaçãoRESUMO
Heterosis has been widely used in multiple crops. However, the molecular mechanism and prediction of heterosis remains elusive. We generated five F1 hybrids [four showing better-parent heterosis (BPH) and one showing mid-parent heterosis], and performed the transcriptomic and methylomic analyses to identify the candidate genes for BPH and explore the molecular mechanism of heterosis and the potential predictors for heterosis. Transcriptomic results showed that most of the differentially expressed genes shared in the four better-parent hybrids were significantly enriched into the terms of molecular function, and the additive and dominant effects played crucial roles for BPH. DNA methylation level, especially in CG context, significantly and positively correlated with grain yield per plant. The ratios of differentially methylated regions in CG context in exons to transcription start sites between the parents exhibited significantly negative correlation with the heterosis levels of their hybrids, as was further confirmed in 24 pairwise comparisons of other rice lines, implying that this ratio could be a feasible predictor for heterosis level, and this ratio of less than 5 between parents in early growth stages might be a critical index for judging that their F1 hybrids would show BPH. Additionally, we identified some important genes showing differential expression and methylation, such as OsDCL2, Pi5, DTH2, DTH8, Hd1 and GLW7 in the four better-parent hybrids as the candidate genes for BPH. Our findings helped shed more light on the molecular mechanism and heterosis prediction.
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Oryza , Humanos , Perfilação da Expressão Gênica , Vigor Híbrido/genética , Oryza/genética , Transcriptoma/genéticaRESUMO
Previous studies have shown that epigenetic factors are involved in the occurrence and development of rheumatoid arthritis (RA). However, the role of N6-methyladenosine (m6A) methylation in RA has not been determined. The aim of this study was to investigate the role and regulatory mechanisms of hypoxia-induced expression of the m6A demethylase alkB homolog 5 (ALKBH5) in RA fibroblast-like synoviocytes (FLSs). Synovial tissues were collected from RA and osteoarthritis (OA) patients, and RA FLSs were obtained. ALKBH5 expression in RA FLSs and collagen-induced arthritis (CIA) model rats was determined using quantitative reverse transcription-PCR (qRT-PCR), western blotting and immunohistochemistry (IHC). Using ALKBH5 overexpression and knockdown, we determined the role of ALKBH5 in RA FLS aggression and inflammation. The role of ALKBH5 in RA FLS regulation was explored using m6A-methylated RNA sequencing and methylated RNA immunoprecipitation coupled with quantitative real-time PCR. The expression of ALKBH5 was increased in RA synovial tissues, CIA model rats and RA FLSs, and a hypoxic environment increased the expression of ALKBH5 in FLSs. Increased expression of ALKBH5 promoted the proliferation and migration of RA-FLSs and inflammation. Conversely, decreased ALKBH5 expression inhibited the migration of RA-FLSs and inflammation. Mechanistically, hypoxia-induced ALKBH5 expression promoted FLS aggression and inflammation by regulating CH25H mRNA stability. Our study elucidated the functional roles of ALKBH5 and mRNA m6A methylation in RA and revealed that the HIF1α/2α-ALKBH5-CH25H pathway may be key for FLS aggression and inflammation. This study provides a novel approach for the treatment of RA by targeting the HIF1α/2α-ALKBH5-CH25H pathway.
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Adenina/análogos & derivados , Agressão , Artrite Reumatoide , Humanos , Ratos , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Inflamação/metabolismo , Hipóxia , Fibroblastos/metabolismo , Proliferação de Células , Células Cultivadas , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismoRESUMO
COLD is a major naturally occurring stress that usually causes complex symptoms and severe yield loss in crops. R-loops function in various cellular processes, including development and stress responses, in plants. However, how R-loops function in COLD responses is largely unknown in COLD susceptible crops like rice (Oryza sativa L.). We conducted DRIP-Seq along with other omics data (RNA-Seq, DNase-Seq and ChIP-Seq) in rice with or without COLD treatment. COLD treatment caused R-loop reprogramming across the genome. COLD-biased R-loops had higher GC content and novel motifs for the binding of distinct transcription factors (TFs). Moreover, R-loops can directly/indirectly modulate the transcription of a subset of COLD-responsive genes, which can be mediated by R-loop overlapping TF-centered or cis-regulatory element-related regulatory networks and lncRNAs, accounting for c. 60% of COLD-induced expression of differential genes in rice, which is different from the findings in Arabidopsis. We validated two R-loop loci with contrasting (negative/positive) roles in the regulation of two individual COLD-responsive gene expression, as potential targets for enhanced COLD resistance. Our study provides detailed evidence showing functions of R-loop reprogramming during COLD responses and provides some potential R-loop loci for genetic and epigenetic manipulation toward breeding of rice varieties with enhanced COLD tolerance.
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Arabidopsis , Oryza , Oryza/metabolismo , Estruturas R-Loop , Proteínas de Plantas/metabolismo , Melhoramento Vegetal , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Temperatura BaixaRESUMO
Both genetic and epigenetic information must be transferred from mother to daughter cells during cell division. The mechanisms through which information about chromatin states and epigenetic marks like histone 3 lysine 27 trimethylation (H3K27me3) are transferred have been characterized in animals; these processes are less well understood in plants. Here, based on characterization of a dwarf rice (Oryza sativa) mutant (dwarf-related wd40 protein 1, drw1) deficient for yeast CTF4 (CHROMOSOME TRANSMISSION FIDELITY PROTEIN 4), we discovered that CTF4 orthologs in plants use common cellular machinery yet accomplish divergent functional outcomes. Specifically, drw1 exhibited no flowering-related phenotypes (as in the putatively orthologous Arabidopsis thaliana eol1 mutant), but displayed cell cycle arrest and DNA damage responses. Mechanistically, we demonstrate that DRW1 sustains normal cell cycle progression by modulating the expression of cell cycle inhibitors KIP-RELATED PROTEIN 1 (KRP1) and KRP5, and show that these effects are mediated by DRW1 binding their promoters and increasing H3K27me3 levels. Thus, although CTF4 orthologs ENHANCER OF LHP1 1 (EOL1) in Arabidopsis and DRW1 in rice are both expressed uniquely in dividing cells, commonly interact with several Polycomb complex subunits, and promote H3K27me3 deposition, we now know that their regulatory functions diverged substantially during plant evolution. Moreover, our work experimentally illustrates specific targets of CTF4/EOL1/DRW1, their protein-proteininteraction partners, and their chromatin/epigenetic effects in plants.
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Arabidopsis/metabolismo , Proteínas de Ligação a DNA/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos , Núcleo Celular/metabolismo , Dano ao DNA , DNA Polimerase I/metabolismo , Flores/fisiologia , Histonas/metabolismo , Lisina/metabolismo , Metilação , Mutação/genética , Oryza/anatomia & histologia , Oryza/citologia , Fenótipo , Proteínas de Plantas/genética , Ligação Proteica , Fase SRESUMO
The testing and evaluation of catalysts in CO2 electroreduction is a very tedious process. To study the catalytic system of CO2 reduction more quickly and efficiently, it is necessary to establish a method that can detect multiple catalysts at the same time. Herein, a series of CuBi bimetallic catalysts have been successfully prepared on a single glass carbon electrode by a scanning micropieptte contact method. The application of scanning electrochemical microscopy (SECM) enabled the visualization of the CO2 reduction activity in diverse catalyst micro-points. The SECM imaging with Substrate generation/tip collection (SG/TC) mode was conducted on CuBi bimetallic micro-points, revealing that HER reaction emerged as the prevailing reaction when a low overpotential was employed. While the applied potential was lower than -1.5 V (vs Ag/AgCl), the reduction of CO2 to formic acid became dominant. Increasing the bismuth proportion in the bimetallic catalyst can inhibit the hydrogen evolution reaction at low potential and enhances the selectivity of the CO product at high cathode overpotential.This research offers a novel approach to examining arrays of catalysts for CO2 reduction.
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Unnatural product (uNP) nonribosomal peptides promise to be a valuable source of pharmacophores for drug discovery. However, the extremely large size and complexity of the nonribosomal peptide synthetase (NRPS) enzymes pose formidable challenges to the production of such uNPs by combinatorial biosynthesis and synthetic biology. Here we report a new NRPS dissection strategy that facilitates the engineering and heterologous production of these NRPSs. This strategy divides NRPSs into "splitting units", each forming an enzyme subunit that contains catalytically independent modules. Functional collaboration between the subunits is then facilitated by artificially duplicating, at the N-terminus of the downstream subunit, the linker - thiolation domain - linker fragment that is resident at the C-terminus of the upstream subunit. Using the suggested split site that follows a conserved motif in the linker connecting the adenylation and the thiolation domains allows cognate or chimeric splitting unit pairs to achieve productivities that match, and in many cases surpass those of hybrid chimeric enzymes, and even those of intact NRPSs, upon production in a heterologous chassis. Our strategy provides facile options for the rational engineering of fungal NRPSs and for the combinatorial reprogramming of nonribosomal peptide production.
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Peptídeo Sintases , Engenharia de Proteínas , Peptídeo Sintases/metabolismo , Peptídeo Sintases/química , Peptídeo Sintases/genética , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismoRESUMO
Plant height is an important agronomic trait that affects crop yield. Elucidating the molecular mechanism underlying plant height regulation is also an important question in developmental biology. Here, we report that a BELL transcription factor, ZmBELL10, positively regulates plant height in maize (Zea mays). Loss of ZmBELL10 function resulted in shorter internodes, fewer nodes, and smaller kernels, while ZmBELL10 overexpression increased plant height and hundred-kernel weight. Transcriptome analysis and chromatin immunoprecipitation followed by sequencing showed that ZmBELL10 recognizes specific sequences in the promoter of its target genes and activates cell division- and cell elongation-related gene expression, thereby influencing node number and internode length in maize. ZmBELL10 interacted with several other ZmBELL proteins via a spatial structure in its POX domain to form protein complexes involving ZmBELL10. All interacting proteins recognized the same DNA sequences, and their interaction with ZmBELL10 increased target gene expression. We identified the key residues in the POX domain of ZmBELL10 responsible for its protein-protein interactions, but these residues did not affect its transactivation activity. Collectively, our findings shed light on the functions of ZmBELL10 protein complexes and provide potential targets for improving plant architecture and yield in maize.
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Perfilação da Expressão Gênica , Zea mays , Zea mays/genética , Zea mays/metabolismo , Ativação Transcricional/genética , Fenótipo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Two-dimensional (2D) p-n heterojunctions have attracted great attention due to their outstanding properties in electronic and optoelectronic devices, especially in photodetectors. Various types of heterojunctions have been constituted by mechanical exfoliation and stacking. However, achieving controlled growth of heterojunction structures remains a tremendous challenge. Here, we employed a two-step KI-assisted confined-space chemical vapor deposition method to prepare multilayer WSe2/SnS2p-n heterojunctions. Optical characterization results revealed that the prepared WSe2/SnS2vertical heterostructures have clear interfaces as well as vertical heterostructures. The electrical and optoelectronic properties were investigated by constructing the corresponding heterojunction devices, which exhibited good rectification characteristics and obtained a high detectivity of 7.85 × 1012Jones and a photoresponse of 227.3 A W-1under visible light irradiation, as well as a fast rise/fall time of 166/440µs. These remarkable performances are likely attributed to the ultra-low dark current generated in the depletion region at the junction and the high direct tunneling current during illumination. This work demonstrates the value of multilayer WSe2/SnS2heterojunctions for applications in high-performance photodetectors.
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Epigenetic modifications, including chromatin modifications and DNA methylation, have a central role in the regulation of gene expression in plants and animals. The transmission of epigenetic marks is crucial for certain genes to retain cell lineage-specific expression patterns and maintain cell fate. However, the marks that have accumulated at regulatory loci during growth and development or in response to environmental stimuli need to be deleted in gametes or embryos, particularly in organisms such as plants that do not set aside a germ line, to ensure the proper development of offspring. In Arabidopsis thaliana, prolonged exposure to cold temperatures (winter cold), in a process known as vernalization, triggers the mitotically stable epigenetic silencing of the potent floral repressor FLOWERING LOCUS C (FLC), and renders plants competent to flower in the spring; however, this silencing is reset during each generation. Here we show that the seed-specific transcription factor LEAFY COTYLEDON1 (LEC1) promotes the initial establishment of an active chromatin state at FLC and activates its expression de novo in the pro-embryo, thus reversing the silenced state inherited from gametes. This active chromatin state is passed on from the pro-embryo to post-embryonic life, and leads to transmission of the embryonic memory of FLC activation to post-embryonic stages. Our findings reveal a mechanism for the reprogramming of embryonic chromatin states in plants, and provide insights into the epigenetic memory of embryonic active gene expression in post-embryonic phases, through which an embryonic factor acts to 'control' post-embryonic development processes that are distinct from embryogenesis in plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cromatina/genética , Cromatina/metabolismo , Temperatura Baixa , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Estações do Ano , Sementes/embriologia , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismoRESUMO
BACKGROUND: Root development and function have central roles in plant adaptation to the environment. The modification of root traits has additionally been a major driver of crop performance since the green revolution; however, the molecular underpinnings and the regulatory programmes defining root development and response to environmental stress remain largely unknown. Single-cell reconstruction of gene regulatory programmes provides an important tool to understand the cellular phenotypic variation in complex tissues and their response to endogenous and environmental stimuli. While single-cell transcriptomes of several plant organs have been elucidated, the underlying chromatin landscapes associated with cell type-specific gene expression remain largely unexplored. RESULTS: To comprehensively delineate chromatin accessibility during root development of an important crop, we applied single-cell ATAC-seq (scATAC-seq) to 46,758 cells from rice root tips under normal and heat stress conditions. Our data revealed cell type-specific accessibility variance across most of the major cell types and allowed us to identify sets of transcription factors which associate with accessible chromatin regions (ACRs). Using root hair differentiation as a model, we demonstrate that chromatin and gene expression dynamics during cell type differentiation correlate in pseudotime analyses. In addition to developmental trajectories, we describe chromatin responses to heat and identify cell type-specific accessibility changes to this key environmental stimulus. CONCLUSIONS: We report chromatin landscapes during rice root development at single-cell resolution. Our work provides a framework for the integrative analysis of regulatory dynamics in this important crop organ at single-cell resolution.
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Meristema , Oryza , Cromatina/genética , Oryza/genéticaRESUMO
The roots of legume plant play a crucial role in nitrogen fixation. However, the transcriptomes of different cell types of legume root and their functions remain largely unknown. Here, we performed single-cell RNA sequencing and profiled more than 22,000 single cells from root tips of Lotus japonicus, a model species of legume. We identified seven clusters corresponding to seven major cell types, which were validated by in situ hybridization. Further analysis revealed regulatory programs including phytohormone and nodulation associated with specific cell types, and revealed conserved and diverged features for the cell types. Our results represent the first single-cell resolution transcriptome for legume root tips and a valuable resource for studying the developmental and physiological functions of various cell types in legumes.
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Lotus , Lotus/genética , Lotus/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Análise da Expressão Gênica de Célula Única , Simbiose/genética , Fixação de Nitrogênio/genética , Nódulos Radiculares de Plantas/genética , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Two-dimensional (2D) materials including black phosphorus (BP) have been extensively investigated because of their exotic physical properties and potential applications in nanoelectronics and optoelectronics. Fabricating BP based devices is challenging because BP is extremely sensitive to the external environment, especially to the chemical contamination during the lithography process. The direct evaporation through shadow mask technique is a clean method for lithography-free electrode patterning of 2D materials. Herein, we employ the lithography-free evaporation method for the construction of BP based field-effect transistors and photodetectors and systematically compare their performances with those of BP counterparts fabricated by conventional lithography and transfer electrode methods. The results show that BP devices fabricated by direct evaporation method possess higher mobility, faster response time, and smaller hysteresis than those prepared by the latter two methods. This can be attributed to the clean interface between BP and evaporated-electrodes as well as the lower Schottky barrier height of 20.2 meV, which is given by the temperature-dependent electrical results. Furthermore, the BP photodetectors exhibit a broad-spectrum response and polarization sensitivity. Our work elucidates a universal, low-cost and high-efficiency method to fabricate BP devices for optoelectronic applications.
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BACKGROUND: The three-dimensional spatial organization of the genome plays important roles in chromatin accessibility and gene expression in multiple biological processes and has been reported to be altered in response to environmental stress. However, the functional changes in spatial genome organization during environmental changes in crop plants are poorly understood. RESULTS: Here we perform Hi-C, ATAC-seq, and RNA-seq in two agronomically important rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica), to report a comprehensive profile of nuclear dynamics during heat stress (HS). We show that heat stress affects different levels of chromosome organization, including A/B compartment transition, increase in the size of topologically associated domains, and loss of short-range interactions. The chromatin architectural changes were associated with chromatin accessibility and gene expression changes. Comparative analysis revealed that 93-11 exhibited more dynamic gene expression and chromatin accessibility changes, including HS-related genes, consistent with observed higher HS tolerance in this cultivar. CONCLUSIONS: Our data uncovered higher-order chromatin architecture as a new layer in understanding transcriptional regulation in response to heat stress in rice.
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Cromatina/química , Genoma de Planta/fisiologia , Resposta ao Choque Térmico/genética , Oryza/genética , Proteínas de Plantas/química , Oryza/fisiologiaRESUMO
The controllable large-area growth of single-crystal vertical heterostructures based on 2D transition metal dichalcogenides (TMDs) remains a challenge. Here, large-area vertical MoS2 /WS2 heterostructures are synthesized using single-step confined-space chemical vapor epitaxy. The heterostructures can evolve into two different kinds by switching the H2 flow on and off: MoS2 /WS2 heterostructures with multiple WS2 domains can be achieved without introducing the H2 flow due to the numerous nucleation centers on the bottom MoS2 monolayer during the transition stage between the MoS2 and WS2 monolayer growth. In contrast, isolated MoS2 /WS2 heterostructures with single WS2 domain can be obtained with introducing the H2 flow due to the reduced nucleation centers on the bottom MoS2 monolayer arising from the hydrogen etching effect. Both the two kinds of the vertical MoS2 /WS2 heterostructures feature high quality. The photodetectors based on the isolated MoS2 /WS2 heterostructures exhibit a high responsivity of 68 mA W-1 and a short response time of 35 ms. This single-step chemical vapor epitaxy can be used to synthesize vertical MoS2 /WS2 heterostructures with high production efficiency. The new epitaxial growth approach may open new pathways to fabricate large-area heterostructures made of different 2D TMDs monolayers of interest to electronics, optoelectronics, and other applications.
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Epigenetic modifications function in gene transcription, RNA metabolism, and other biological processes. However, multiple factors currently limit the scientific utility of epigenomic datasets generated for plants. Here, using deep-learning approaches, we developed a Smart Model for Epigenetics in Plants (SMEP) to predict six types of epigenomic modifications: DNA 5-methylcytosine (5mC) and N6-methyladenosine (6mA) methylation, RNA N6-methyladenosine (m6 A) methylation, and three types of histone modification. Using the datasets from the japonica rice Nipponbare, SMEP achieved 95% prediction accuracy for 6mA, and also achieved around 80% for 5mC, m6 A, and the three types of histone modification based on the 10-fold cross-validation. Additionally, > 95% of the 6mA peaks detected after a heat-shock treatment were predicted. We also successfully applied the SMEP for examining epigenomic modifications in indica rice 93-11 and even the B73 maize line. Taken together, we show that the deep-learning-enabled SMEP can reliably mine epigenomic datasets from diverse plants to yield actionable insights about epigenomic sites. Thus, our work opens new avenues for the application of predictive tools to facilitate functional research, and will almost certainly increase the efficiency of genome engineering efforts.
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Aprendizado Profundo , Oryza , Metilação de DNA/genética , Epigênese Genética , Epigenômica , Genoma , Oryza/genéticaRESUMO
We aimed to investigate the expression level of long noncoding RNA (lncRNA) zinc finger E-box-binding homeobox two antisense RNA 1 (ZEB2-AS1) in osteosarcoma and explore its possible regulatory mechanisms. Expression of lncRNA ZEB2-AS1 was detected by quantitative real-time PCR in 63 cancerous tissues and 25 adjacent normal mucosal tissues from patients with osteosarcoma. The correlation between the lncRNA ZEB2-AS1 level and clinicopathological characteristics of the osteosarcoma patients were evaluated, and 5-year overall survival (5OS) was also analyzed according to lncRNA ZEB2-AS1 expression. The ZEB2-AS1 and miR-145 recombinant expression vector was used to analyze their relationship in an in vitro cell system. Luciferase reporter gene assays and RNA immunoprecipitation assays were used to verify the interaction between ZEB2-AS1 and miR-145. The proliferation, apoptosis and migration of osteosarcoma cells were determined by Cell counting kit-8 assays, Annexin V-PI assays and transwell assays, respectively. A significantly increased level of lncRNA ZEB2-AS1 with a fold change of 3.86 was found in osteosarcoma tissues compared with control tissues (P < 0.001). The Chi-square test revealed that lncRNA ZEB2-AS1 expression in osteosarcoma was significantly different according to radiology classification (P = 0.018), TNM stage (P = 0.000) and survival status (P = 0.005). The 5OS was 18.4% and 52% in osteosarcoma patients with higher and lower lncRNA ZEB2-AS1 expression, respectively. Significantly increased ZEB2-AS1 expression was found in osteosarcoma cells, while decreased levels of miR-145 were confirmed in osteosarcoma tissues and cell lines compared to controls. Moreover, a negative correlation was found between the expression level of ZEB2-AS1 and miR-145 in osteosarcoma tissues (R2 = 0.71, P < 0.01). ZEB2-AS1 knockdown resulted in decreased osteosarcoma cell proliferation, increased apoptosis and reduced migration. In addition, negative regulation of miR-145 by ZEB2-AS1 in osteosarcoma cells was also observed, and the effects of ZEB2-AS1 on osteosarcoma cells were found to be regulated by miR-145. Significantly upregulated lncRNA ZEB2-AS1 expression in osteosarcoma patients influences the prognosis of patients, and ZEB2-AS1 accelerates tumorigenesis and osteosarcoma development by downregulating miR-145.
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Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/genética , RNA Longo não Codificante/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Adolescente , Adulto , Idoso , Apoptose , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Criança , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/mortalidade , Osteossarcoma/patologia , RNA Antissenso , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida , Regulação para Cima , Adulto JovemRESUMO
Alloy engineering is efficient in modulating the electronic structure and physical and chemical properties of Transition metal dichalcogenides (TMDs). Here, we develop an efficient and simple confined-space CVD strategy by using a smaller quartz boat nested in a larger quartz boat for the preparation of ternary alloy MoS2(1-x)Se2xmonolayers on SiO2/Si substrates with controllable composition. The effect of hydrogen ratio of the mixed carrier gas (Ar/H2) on the resultant flakes are systematically investigated. A hydrogon ratio of 15% is demonstrated to be the most appropriate to synthesize large size (more than 400µm) single crystalline MoS2(1-x)Se2xalloy monolayers. The composition of the alloy can also be changed in a full range (2x= 0-2) by changing the weight ratio of Se and S powder. The as-grown monolayer MoS2(1-x)Se2xalloys present continuously high crystal quality in terms of Raman and PL measurements. Furthermore, to visible light (532 nm), the MoS2(1-x)Se2xbased photodetectors display wonderful photoresponse with a fast response of less than 50 ms. Our work may be usedful in directing the synthesis of TMDs alloys as well as their optoelectronic applications.
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In recent years, two-dimensional materials have received more and more attention in the development of semiconductor devices, and their practical applications in optoelectronic devices have also developed rapidly. However, there are still some factors that limit the performance of two-dimensional semiconductor material devices, and one of the most important is Ohmic contact. Here, we elaborate on a variety of approaches to achieve Ohmic contacts on two-dimensional materials and reveal their physical mechanisms. For the work function mismatch problem, we summarize the comparison of barrier heights between different metals and 2D semiconductors. We also examine different methods to solve the problem of Fermi level pinning. For the novel 2D metal-semiconductor contact methods, we analyse their effects on reducing contact resistance from two different perspectives: homojunction and heterojunction. Finally, the challenges of 2D semiconductors in achieving Ohmic contacts are outlined.