- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Adipose Tissue and Metabolism
- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Gene Regulatory Network Analysis
- Plant-Microbe Interactions and Immunity
- Histone Deacetylase Inhibitors Research
- Genomics and Phylogenetic Studies
- Pancreatic function and diabetes
- Oxidative Organic Chemistry Reactions
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- RNA Research and Splicing
- Parallel Computing and Optimization Techniques
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Reactions
- Plant Pathogens and Fungal Diseases
- Advanced Proteomics Techniques and Applications
- Folate and B Vitamins Research
- Fungal Biology and Applications
- Genetics and Neurodevelopmental Disorders
Jiangsu Province Hospital
2022-2024
Nanjing Medical University
2022-2024
Jilin University
2013-2024
Chinese PLA General Hospital
2023
Michigan State University
2004-2023
Shanghai Institute of Organic Chemistry
2016-2023
University of Chinese Academy of Sciences
2020-2023
Southern University of Science and Technology
2023
Fudan University
2023
Sichuan University
2023
The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which partially converted 5-hydroxymethylcytosine (5hmC) by Tet (ten eleven translocation) family dioxygenases. Despite their importance epigenetic regulation, it unclear how these modifications are reversed. Here, we demonstrate that 5mC and 5hmC oxidized 5-carboxylcytosine (5caC) dioxygenases vitro cultured cells. 5caC specifically recognized excised thymine-DNA glycosylase (TDG)....
DNA hydroxymethylation and its mediated demethylation are critical for multiple cellular processes, example, nuclear reprogramming, embryonic development, many diseases. Here, we demonstrate that a vital nutrient ascorbic acid (AA), or vitamin C (Vc), can directly enhance the catalytic activity of Tet dioxygenases oxidation 5-methylcytosine (5mC). As evidenced by changes in intrinsic fluorescence Tet2 protein caused AA oxidation-resistant derivatives, further show uniquely interact with...
Abstract Hornworts comprise a bryophyte lineage that diverged from other extant land plants >400 million years ago and bears unique biological features, including distinct sporophyte architecture, cyanobacterial symbiosis pyrenoid-based carbon-concentrating mechanism (CCM). Here, we provide three high-quality genomes of Anthoceros hornworts. Phylogenomic analyses place hornworts as sister clade to liverworts plus mosses with high support. The lack repeat-dense centromeres well...
Genetic drivers of cancer can be dysregulated through epigenetic modifications DNA. Although the critical role DNA 5-methylcytosine (5mC) in regulation transcription is recognized, functions other non-canonical remain obscure. Here, we report identification novel N6-methyladenine (N6-mA) human tissues and implicate this mark disease, specifically highly malignant brain glioblastoma. Glioblastoma markedly upregulated N6-mA levels, which co-localized with heterochromatic histone modifications,...
The combination of Cu(acac)2 and N,N'-bis(4-hydroxyl-2,6-dimethylphenyl)oxalamide (BHMPO) provides a powerful catalytic system for hydroxylation (hetero)aryl halides. A wide range chlorides bearing either electron-donating or -withdrawing groups proceeded well at 130 °C, delivering the corresponding phenols hydroxylated heteroarenes in good to excellent yields. When more reactive bromides iodides were employed, reactions completed relatively low temperatures (80 60 respectively) loadings...
In Magnaporthe grisea, a well-conserved mitogen-activated protein (MAP) kinase gene, PMK1, is essential for fungal pathogenesis. this study, we tested whether the same MAP plant infection in gray mold fungus Botrytis cinerea, necrotrophic pathogen that employs mechanisms different from those of M. grisea. We used polymerase chain reaction-based approach to isolate homologues B. cinerea. The required pathogenesis (BMP) gene highly homologous grisea PMK1. BMP1 single-copy gene. bmp1...
In the rice blast fungus Magnaporthe grisea, a mitogen-activated protein kinase gene, PMK1, is known to regulate ap-pressorium formation and infectious hyphae growth. Since PMK1 homologous FUS3 KSS1 genes that transcription factor STE12 in yeast, we functionally characterized homologue M. grisea (MST12). A polymerase chain reaction-based approach was used isolate MST12 gene yeast STE12. Four mst12 deletion mutants were isolated by replacement. No obvious defect vegetative growth,...
We report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized full-length isoform containing an N-terminal CXXC domain (Tet3FL). This binds to unmethylated CpGs, but, unexpectedly, its highest affinity is toward 5-carboxylcytosine (5caC). determined crystal structure of domain-5caC-DNA complex, revealing structural basis binding specificity this a reader CcaCG sequences. Mapping Tet3FL in neuronal cells shows localized precisely at...
Abstract N 6 -methyladenine ( -mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels -mA undergo drastic fluctuation during early embryogenesis, indicative active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser unpairing regions (e.g., SIDD, S tress- I nduced D NA Double Helix estabilization regions) genomes. Enzymatic profiling studies revealed prefers bubbled or bulged DNAs substrate, instead single-stranded (ss-)...
Abstract Primary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% cases, with high disability and mortality rate. Early brain injury (EBI) critical factor in determining SAH mortality; however, there are no effective treatment interventions EBI. Based on our results, the transmission cyclic GMP-AMP (cGAMP) from neurons to microglia key molecular event that triggers I interferon response, amplifies neuroinflammation, leads neuronal apoptosis. Abnormal...
The PMK1 mitogen-activated protein kinase gene regulates appressorium formation and infectious hyphae growth in the rice blast fungus. To further characterize this pathway, we constructed a subtraction library enriched for genes regulated by PMK1. Two identified library, GAS1 GAS2, encode small proteins that are homologous with gEgh16 of powdery mildew Both were expressed specifically during wild-type strains, but neither was pmk1 mutant. Mutants deleted GAS2 had no defect vegetative growth,...
ABSTRACT The role of bacteria in the occasional emergence red water, which has been documented worldwide, yet to be determined. To better understand mechanisms that drive occurrences bacterial community composition and relative abundance several functional groups a water distribution system Beijing during large-scale event were determined using molecular methods. Individual clone libraries 16S rRNA gene constructed for three samples one sample normal water. Beta -, Alpha Gammaproteobacteria...
Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation vertebrates. However, it remained unclear how they contribute to the process. Here, we demonstrate that Gadd45a promotes active through thymine glycosylase (TDG) which has recently shown excise 5-formylcytosine (5fC) 5-carboxylcytosine (5caC) generated Ten-eleven-translocation (Tet)—initiated oxidative demethylation. The connection of with is evidenced by enhanced activation a...
Therapeutic monoclonal antibodies against the PD-L1/PD-1 (programmed death ligand-1/programmed cell protein-1) axis have achieved great successes in cancer treatments, but development of small-molecule immunomodulators pathway has lagged far behind. We established a cellular coculture assay with two stable transfectant lines, PD-L1-expressing tumor line PC9/PD-L1 and PD-1-expressing T Jurkat/PD-1. Western blotting analyses were used to monitor interaction signaling. analyzed PD-L1...
Abstract Aminoacyl-tRNA synthetases (AARSs), a family of essential protein synthesis enzymes, are attractive targets for drug development. Although several different types AARS inhibitors have been identified, covalent not reported. Here we present five unusual crystal structures showing that threonyl-tRNA synthetase (ThrRS) is covalently inhibited by natural product, obafluorin (OB). The residue forming bond with OB tyrosine in ThrRS active center, which commonly modified inhibitors. two...
Dynamic protein-protein interactions (PPIs) play crucial roles in cell physiological processes. The protein-fragment complementation (PFC) assay has been developed as a powerful approach for the detection of PPIs, but its potential identifying protein interacting regions is not optimized. Recently, an ascorbate peroxidase (APEX2)-based proximity-tagging method combined with mass spectrometry was to identify live cells. In this study, we tested whether APEX2 could be employed PFC. By...
Significance Understanding how clathrin-independent endocytic (CIE) cargo proteins are sorted into and transported within endosomes has attracted growing interests. Here, in Caenorhabditis elegans intestine, a well-established genetic system for deciphering trafficking multicellular organisms, we report direct visualization of dynamic endosomal tubules as carriers basolateral recycling certain CIE cargoes. We unveil the coordination Rab GTPase RAB-10, exocyst component SEC-10, microtubule...
In a gene regulatory network, genes are typically regulated by transcription factors (TFs). Transcription factor activity (TFA) is more difficult to measure than expression levels are. Other models have extracted information about TFA from data, but without explicitly modeling feedback the genes. We present state-space model (SSM) with hidden variables. The variables include motifs in such as loops and auto-regulation, making SSM useful complement existing models.A network incorporating, for...
Aminoacyl-tRNA synthetases are attractive targets for the development of antibacterial, antifungal, antiparasitic agents and treatment other human diseases. Lysyl-tRNA synthetase (LysRS) from this family has been validated as a promising target antimalarial drugs. Here, we developed high-throughput compatible assay screened 1215 bioactive compounds to identify Plasmodium falciparum cytoplasmic LysRS (PfLysRS) inhibitor. ASP3026, an anaplastic lymphoma kinase inhibitor that was used in...