Biology subjects

Zong, Z.

Publications and source records attributed to Zong, Z..

9 recordsLinked to original sources

bioRxiv2026

GAMETE maps the genetic architecture of chromatin accessibility in rice pollen at single-nucleus resolution

BackgroundDissecting the genetic basis of cell-type-specific gene regulation during gametogenesis remains a major challenge. Population-level studies mask cellular heterogeneity, while the extreme data sparsity of single-cell profiling has precluded robust genetic mapping. ResultsWe present GAMETE (Genetic Architecture Mapping of Epigenetic Traits at single-nucleus resolution), an integrated framework combining MPS-ATAC-seq, a high-throughput single-nucleus ATAC-seq method, with robust computational approaches for genotype inference and genetic mapping from sparse single-nucleus data. Applying GAMETE to hybrid rice pollen, we simultaneously profiled chromatin accessibility and inferred the genotypes of 4,887 individual haploid nuclei, revealing distinct chromatin landscapes across pollen cell types. This uncovered an unexpected elevation of chromatin accessibility at gypsy retrotransposons in microspores preceding their silencing in sperm cells, exposing a surveillance gap that may contribute to genome expansion. The synchronized profiling enabled us to construct a single-cell recombination map, map segregation distortion loci and trace their developmental origins, and identify 16,113 chromatin accessibility QTLs (caQTLs), 48.6% of which exhibited pronounced cell-type specificity. Analysis of introgression lines supported a cell-type-specific trans-acting caQTL regulating the pollen-essential gene DTM1. ConclusionsThis work establishes GAMETE as a broadly applicable framework for dissecting the genetic architecture of chromatin accessibility during gametogenesis without the need for subsequent generations.

genomics↗

bioRxiv2026

ISPpu10 is a structure-gated bridge RNA recombinase that drives safe, large-scale genomic plasticity

IS110 elements employ bridge RNA to direct target site recognition, yet whether additional layers of specificity exist beyond RNA-DNA base pairing is unknown. Here we identified ISPpu10, an IS110 element in Pseudomonas putida that is associated with >100-kb segmental amplifications during adaptive laboratory evolution. All insertions mapped to multiple identical copies of a single conserved intergenic sequence harboring a GC-rich 5' extension that forms a stem-loop. Systematic mismatch and compensatory substitution scanning revealed a sequence-structure dual-match logic: base pairing between the bridge RNA and target DNA serves as an RNA-guided match, whereas the target-encoded stem-loop provides an additional specificity determinant. Transplanting this stem-loop into Escherichia coli targets improved on-target integration and reduced genome-wide off-target insertion, establishing the stem-loop as a portable structural gate. These findings reveal a structural recognition layer beyond base-pairing, suggesting how bacteria reconcile transposition with genome integrity and offering a strategy for precise genome editing.

microbiology↗

bioRxiv2026

Uncompetitive Allosteric Inhibitor of Mitochondrial Creatine Kinase Prevents Binding and Release of Creatine by Stabilization of Loop Closure

Mitochondrial creatine kinase (MtCK) is a key enzyme in energy buffering and homeostasis in cells. It catalyzes transfer of phosphoryl group from ATP to creatine. Overexpression of MtCK occurs in many cancer cells to meet elevated energy demands, which is associated with poor prognosis. This suggests that MtCK may be a promising target for cancer therapeutics. We sought to discover first-in-class selective inhibitors of MtCK with diverse mechanisms of action using high-throughput screening, biochemical characterization and cryo-EM studies. Through these studies, we identified diverse types of compounds that modulate activity of MtCK in vitro, including fast-equilibrium and time-dependent orthosteric and allosteric inhibitors. Select hits were subjected to in vitro enzymatic and binding assays to assess MtCK inhibition and binding. A subset of inhibitors was advanced into structural studies using cryo-EM resulting in the molecular structure of MtCK with and without bound substrates in complex with an allosteric uncompetitive inhibitor that we discovered. These studies identified compounds unique binding pocket on MtCK and established the molecular steps manifesting in the apparent uncompetitive mode of inhibition. We demonstrate that the compound stabilizes an active site loop in a closed conformation restricting access of the creatine substrate to and the release of phosphocreatine product from its binding pocket. These findings establish chemical tools suitable for validation of MtCK as a promising breast cancer target with high therapeutic potential and build a foundation for future structure-guided optimization of the hit compounds of MtCK we identified and de novo rational design of novel MtCK inhibitors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/696683v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1fd9870org.highwire.dtl.DTLVardef@230e31org.highwire.dtl.DTLVardef@178d8fdorg.highwire.dtl.DTLVardef@edeca6_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Comprehensive mapping and modelling of the rice regulome landscape unveils the regulatory architecture underlying complex traits

Unraveling the regulatory mechanisms that govern complex traits is pivotal for advancing crop improvement. Here we present a comprehensive regulome atlas for rice (Oryza sativa), charting the chromatin accessibility across 23 distinct tissues from three representative varieties. Our study uncovers 117,176 unique open chromatin regions (OCRs), accounting for [~]15% of the rice genome, a notably higher proportion compared to previous reports in plants. Integrating RNA-seq data from matched tissues, we confidently predict 59,075 OCR-to-gene links, with enhancers constituting 69.54% of these associations, including many known enhancer-to-gene links. Leveraging this resource, we re-evaluate genome-wide association study results and discover a previously unknown function of OsbZIP06 in seed germination, which we subsequently confirm through experimental validation. We optimize deep learning models to decode regulatory grammar, achieving robust modeling of tissue-specific chromatin accessibility. This approach allows to predict cross-variety regulatory dynamics from genomic sequences, shedding light on the genetic underpinnings of cis-regulatory divergence and morphological disparities between varieties. Overall, our study establishes a foundational resource for rice functional genomics and precision molecular breeding, providing valuable insights into regulatory mechanisms governing complex traits.

genomics↗

bioRxiv2022

A novel cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma

BackgroundCuproptosis has recently been considered a novel form of programmed cell death. To date, factors crucial to the regulation of this process remain unelucidated. Here, we aimed to identify long-chain non-coding RNAs (lncRNAs) associated with cuproptosis in order to predict the prognosis of patients with hepatocellular carcinoma (HCC). MethodsUsing RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related mRNAs and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, TMB (tumor mutation burden), and pharmacologic options were made between high- and low-risk groups. ResultsOur prognostic risk model was constructed using the cuproptosis-related PICSAR, FOXD2-AS1, and AP001065.1 lncRNAs. The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95% CI = 1.063- 1.270; p < 0.001). Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as internal validation cohorts. A prognostic nomogram developed considering CupRLSig data and a number of clinical characteristics were found to exhibit adequate performance in survival risk stratification. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses. Finally, differences in immune checkpoint expression and responses to chemotherapy as well as in targeted therapy among CupRLSig stratified high- and low-risk groups were explored. ConclusionsThe lncRNA signature constructed in this study is valuable in prognostic estimation in the setting of HCC.

bioinformatics↗

bioRxiv2020

Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD+, Causes Reductive Stress, and Suppresses Glycolysis and Cell Growth

In the present study, we developed a chemical method to produce dihydro nicotinamide mononucleotide (NMNH), which is the reduced-form of nicotinamide mononucleotide (NMN). We demonstrated that NMNH was a better NAD+ enhancer compared to NMN both in vitro and in vivo mediated by NMNAT. Additionally, NMNH increased the reduced NAD (NADH) levels in cells and in mouse liver. Metabolomic analysis revealed that NMNH inhibited glycolysis and TCA cycle. In vitro experiments demonstrated that NMNH induced cell cycle arrest and suppressed cell growth. Nevertheless, NMNH treatment did not cause observable difference in mice. Taken together, our work demonstrates that NMNH is a potent NAD+ enhancer, and suppresses glycolysis, TCA cycle and cell growth.

biochemistry↗

bioRxiv2019

Description of Klebsiella spallanzanii sp. nov. and of Klebsiella pasteurii sp. nov.

Klebsiella oxytoca causes opportunistic human infections and post-antibiotic haemorrhagic diarrhoea. This Enterobacteriaceae species is genetically heterogeneous and is currently subdivided into seven phylogroups (Ko1 to Ko4, Ko6 to Ko8). Here we investigated the taxonomic status of phylogroups Ko3 and Ko4. Genomic sequence-based phylogenetic analyses demonstrate that Ko3 and Ko4 formed well-defined sequence clusters related to, but distinct from, Klebsiella michiganensis (Ko1), Klebsiella oxytoca (Ko2), K. huaxiensis (Ko8) and K. grimontii (Ko6). The average nucleotide identity of Ko3 and Ko4 were 90.7% with K. huaxiensis and 95.5% with K. grimontii, respectively. In addition, three strains of K. huaxiensis, a species so far described based on a single strain from a urinary tract infection patient in China, were isolated from cattle and human faeces. Biochemical and MALDI-ToF mass spectrometry analysis allowed differentiating Ko3, Ko4 and Ko8 from the other K. oxytoca species. Based on these results, we propose the names Klebsiella spallanzanii for the Ko3 phylogroup, with SPARK_775_C1T (CIP 111695T, DSM 109531T) as type strain, and Klebsiella pasteurii for Ko4, with SPARK_836_C1T (CIP 111696T, DSM 109530T) as type strain. Strains of K. spallanzanii were isolated from human urine, cow faeces and farm surfaces, while strains of K. pasteurii were found in faecal carriage from humans, cows and turtles.\n\nAccession numbersThe nucleotide sequences generated in this study were deposited in ENA and are available through the INSDC databases under accession numbers MN091365 (SB6411T = SPARK775C1T), MN091366 (SB6412 T = SPARK836C1T) and MN104661 to MN104677 (16S rRNA), MN076606 to MN076643 (gyrA and rpoB), and MN030558 to MN030567 (blaOXY). Complete genomic sequences were submitted to European Nucleotide Archive under the BioProject number PRJEB15325.\n\nAbbreviationsANI, average nucleotide identity; HCCA, a-cyano-4-hydroxycinnamic acid; isDDH, in silico DNA-DNA hybridization; SCAI, Simmons citrate agar with inositol; MALDI57 ToF MS: Matrix-assisted laser desorption/ionization time of flight mass spectrometry

microbiology↗

bioRxiv2018

Klebsiella huaxiensis sp. nov., recovered from human urine

A Klebsiella strain, WCHKl090001, was recovered from a human urine sample in China in 2017. Phylogenetic analysis based on gyrA and rpoB housekeeping genes revealed that the strain was distinct from any previously described species of the genus Klebsiella though it was clustered with the Klebsiella oxytoca phylogroup including Klebsiella grimontii, Klebsiella michiganensis, and Klebsiella oxytoca. The whole genome sequence of strain WCHKl090001 has an up to 87.18% average nucleotide identity with those of type strains of all known Klebsiella species. In silico DNA-DNA hybridization (isDDH) values between strain WCHKl090001 and type strains of all known Klebsiella species range from 22.3 to 35.2%. Strain WCHKl090001 could be distinguished from species of the Klebsiella oxytoca phylogroup by its negative Voges-Proskauer reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHKl090001 should be considered to represent a novel species of the genus Klebsiella, for which the name Klebsiella huaxiensis sp. nov. is proposed. The type strain is WCHKl090001T (=GDMCC1.1379T = CCTCC AB 2018106 T).

microbiology↗

bioRxiv2017

New kids on the block: Intercontinental dissemination and transmission of newly emerging lineages of multi-drug resistant Escherichia coli with highly dynamic resistance gene acquisition.

The increase in infections as a result of multi-drug resistant strains of Escherichia coli is a global health crisis. The emergence of globally disseminated lineages of E. coli carrying ESBL genes has been well characterised. An increase in strains producing carbapenemase enzymes and mobile colistin resistance is now being reported, but to date there is little genomic characterisation of such strains. Routine screening of patients within an ICU of West China Hospital identified a number of E. coli carrying the blaNDM-5 carbapenemase gene, found to be two distinct clones, E. coli ST167 and ST617. Interrogation of publically available data shows isolation of ESBL and carbapenem resistant strains of both lineages from clinical cases across the world. Further analysis of a large collection of publically available genomes shows that ST167 and ST617 have emerged in distinct patterns from the ST10 clonal complex of E. coli, but share evolutionary events involving switches in LPS genetics, intergenic regions and anaerobic metabolism loci. These may be evolutionary events which underpin the emergence of carbapenem resistance plasmid carriage in E. coli.

microbiology↗