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Wang, C.

Publications and source records attributed to Wang, C..

At least 217 records · Page 12Linked to original sources
bioRxiv2026

Chromatin context-dependent deacetylation by the asymmetric Rpd3L

The regulation of gene expression requires precise control of chromatin-associated complexes that respond to diverse structural and epigenetic cues. The Rpd3 Large (Rpd3L) complex is a Sin3 histone deacetylase (HDAC) complex that dynamically adapt to chromatin states to reinforce transcriptional silencing, yet the mechanisms governing the catalytic activation in chromatin context-dependent manner remain unclear. Here we present the cryo-EM structure of Rpd3L bound to both mono- and di-nucleosome substrate at near-atomic resolution, uncovering a substrate-guided allosteric activation mechanism. Rpd3L adopts an asymmetric architecture, in which the proximal catalytic module anchors the first nucleosome, while the Sin3 PAH domains engage linker DNA to reposition a second nucleosome. This spatial configuration brings the distal catalytic module into proximity with chromatin and unlocks its latent deacetylase activity. Biochemical and mass spectrometry analyses confirm that dual nucleosome engagement selectively enhances Rpd3L activity and broadens substrate specificity. Together, these findings establish a hierarchical mechanism by which Rpd3L interprets histone modifications and nucleosome organization to modulate its enzymatic output at promoter regions. Our study provides a framework for understanding higher-order chromatin repression mechanisms by chromatin-regulation complexes and co-repressors.

molecular biology↗
bioRxiv2026

IFNγ-Driven Inflammatory Responses in the Nasal Mucosa Drive Influenza Virus Shedding and Transmission

What determines host infectiousness during influenza A virus (IAV) infection remains a fundamental unanswered question in virology. While upper respiratory tract (URT) replication is necessary for transmission, its insufficient to explain host-to-host variation in contagiousness. Using the infant mouse model of influenza transmission, we show that viruses containing H3 hemagglutinin shed at higher levels than non-H3-containing viruses, despite comparable URT replication. H3-containing virus infection was associated with higher URT inflammation, characterized by increased cytokine production, immune cell recruitment, and mucus hypersecretion, which directly correlated with shedding efficiency. Transcriptomic profiling identified enrichment of interferon-stimulated gene programs, with a dominant interferon gamma (IFN{gamma}) signature during H3 infections. Functional studies demonstrated that IFN{gamma} deficiency reduced mucus production, shedding, and transmission, whereas IFN{gamma} supplementation restored these phenotypes. Together, these findings identify IFN{gamma}-driven mucosal inflammation key host determinant of influenza infectiousness, reframing contagiousness as a consequence of host inflammatory clearance rather than viral replication alone.

microbiology↗
bioRxiv2026

Ultra-fast genetic recovery of dead fish through cross-family germline stem cell transplantation

AbstactThe conservation of genetic resources from aquaculture species and endangered fish is increasingly challenged by large body size, long reproductive cycles, and limited opportunities for timely intervention after death. Here, we establish and validate an ultra-fast genetic platform based on germline stem cell transplantation to enable postmortem genetic recovery in fish. Using grass carp (Ctenopharyngodon idella) as a representative warm-water species, we systematically quantified the relationships among postmortem tissue freshness, germline stem cell viability, and transplantation efficiency, and demonstrated that low-temperature preservation plays a decisive role in maintaining germline activity after death. Germline stem cells isolated from deceased grass carp were transplanted into germ-cell-depleted zebrafish recipients, where they rapidly colonized recipient gonads, underwent proliferation and differentiation, and generated functional donor-derived gametes within three months. These gametes supported successful fertilization and normal embryonic development, ultimately yielding viable grass carp offspring. Our results reveal an intrinsic postmortem resilience of germline stem cells and demonstrate that cross-species transplantation into small, fast-maturing hosts can dramatically accelerate genetic recovery. This strategy overcomes key biological and logistical constraints associated with conventional breeding-based rescue approaches and provides a rapid, scalable, and broadly applicable framework for postmortem genetic resource conservation in aquaculture and endangered fish species.

zoology↗
bioRxiv2026

De novo design of metalloproteases for targeted amyloid-β cleavage

De novo protein design has not yet achieved the creation of proteases capable of selectively cleaving any desired peptide bond within a native protein with high precision. Here, we report the use of the flow-based generative model Proteus2 to design metalloproteases by generating enzyme-substrate complexes conditioned on a target peptide sequence and a predefined catalytic motif. Our approach employs a two-step encapsulation strategy to create clamp-like metalloproteases that bind the target peptide in a manner that maximizes substrate sequence specificity. The generative process simultaneously optimizes the precise positioning of the target peptide bond in a catalytically competent configuration and accurately scaffolds the transition state catalytic residues--both essential for specific and efficient catalysis. Using this strategy, we designed zinc metalloproteases targeting three distinct cleavage sites within the aggregation-prone regions of amyloid-{beta} (A{beta}), a key pathogenic factor in Alzheimers disease. Experimental characterization validated five enzymes, each capable of precise cleavage at the intended sites with high specificity and minimal or undetectable activity on non-cognate substrates. On average, these enzymes accelerated peptide bond hydrolysis by more than 107-fold relative to the uncatalyzed reaction, and enabled efficient digestion of the A{beta} peptide into smaller segments when enzymes targeting different sites were combined. Cryo-EM structures of three designed enzymes in complex with A{beta} peptide, each targeting a distinct cleavage site, revealed close agreement with the design models. Together, these results demonstrate the potential of sequence-guided, generative approaches for developing programmable, sequence-specific proteolysis and lay the groundwork for future applications in basic research and therapeutic development.

synthetic biology↗
bioRxiv2026

A panoramic view of the expression and function of the Doublesex/DMRT gene family in C. elegans

Throughout the animal kingdom, sex determination and sexual differentiation are orchestrated by a strikingly diverse set of regulatory factors. The only type of molecules consistently deployed during sexual differentiation are members of the Doublesex/Mab-3-related transcription factor (DMRT) family. Although each animal genome codes for a multitude of DMRT family members, in no species has the full array of DMRT genes been comprehensively analyzed across the entire animal, in all sexes and throughout development. Hence, the extent of deployment of DMRT genes in sexual differentiation remains unknown. We describe here the first genome- and nervous system-wide expression and functional analysis of all members of the DMRT gene family. Leveraging genome-engineered reporter alleles of all ten DMRT genes of the nematode Caenorhabditis elegans, we find that six DMRTs display sexually dimorphic expression in somatic and/or reproductive tissues, including in cell and tissue types not previously known to be sexually dimorphic. In the nervous system, DMRT protein expression covers many, though not all, known sexually dimorphic neuron types. Analyses of DMRT null mutant alleles reveal a suite of neuronal differentiation defects, ranging from altered neurotransmitter identities and switched neuropeptide signatures to impaired glia-to-neuron transdifferentiation. Several DMRT proteins do not exhibit sexually dimorphic expression, indicating roles beyond sexual differentiation. Similar comprehensive analyses of DMRT genes in other organisms may help to better understand the extent and regulation of sex-specific cellular differentiation programs.

developmental biology↗
bioRxiv2025

Senescent host-derived extracellular vesicles potentiate antitumor immunity via bystander T cell activation

Extracellular vesicles (EVs) are key mediators of intercellular communication, and those from the plasma of aged individuals are typically viewed as drivers of aging or even cancer. Here, we uncover a latent, potent antitumor capacity inherent to EVs derived from aged hosts. Specifically, we demonstrate that extracellular vesicles from the plasma of aged mice (A-EVs) exhibit robust tumor-suppressive activity in young tumor-bearing recipients. Mechanistically, A-EVs engage a dual mode of action: they directly induce senescence in cancer cells, enhancing their immunogenicity. More importantly, they concurrently activate non-tumor-specific bystander CD8 T cells within the tumor microenvironment via cross-presentation of pathogen-derived antigens, thereby reshaping the immunosuppressive tumor microenvironment. This synergistic interplay potently reinvigorates antitumor immunity and sensitizes tumors to PD-L1 checkpoint blockade. Our findings establish A-EVs as a novel class of endogenous immunomodulators with broad therapeutic potential for cancer immunotherapy.

immunology↗
bioRxiv2025

Myeloid cells contribute to bystander CD8 T cell accumulation in metabolic-associated steatohepatitis and are sufficient for fibrosis

Background & AimsMetabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver fibrosis, morbidity, and mortality. It is characterized by the accumulation of fat in hepatocytes causing cell death followed by stromal cell activation and scar deposition at later disease stages. While a marked accumulation of cytotoxic CD8 T cells is observed in MASH in humans and mice, the role of adaptive immune cells in fibrosis progression remains debated. MethodsTranscriptional data were curated from human datasets and preclinical mouse models, including mice deficient in TCR{beta} T cells (Tcrb-/-), which lack conventional CD4 helper and CD8 cytotoxic T cells, in diet-induced fibrosing MASH for single-cell RNA-sequencing. Specific human and mouse liver transcriptomic immune signatures were corroborated by flow cytometry and immunofluorescence. ResultsxMASH was associated with the expansion of lymphocytes and myeloid cells. Auto-aggressive CXCR6+PD1+FASLG+ CD8 T cells were enriched in livers of high-fat-diet-fed mice and correlated with MASH and fibrosis. Notably, Tcrb-deficient mice in a chemical and dietary preclinical MASH model developed fibrosis to the same extent as wild-type mice and exhibited exacerbated pro-fibrotic type 3 inflammation. Loss of conventional CD8 T cells neither impacted myeloid cell number nor phenotype within the fibrotic niche. Neutrophil- and non-conventional lymphocyte-derived GM-CSF and IL-17A were central drivers in the fibrotic niche composed of pathogenic macrophages and activated myofibroblasts. Furthermore, myeloid cells were identified as the main source of CXCL16 in diseased livers, retaining auto-aggressive CD8 T cells to the scar and contributing to their accumulation. Thus, non-adaptive cells, including scar-associated macrophages (SAMs) and myofibroblasts, are sufficient for MASH-driven fibrosis in this model. ConclusionsTargeting myeloid cells and fibroblasts should be prioritized as anti-fibrotic therapies for MASH. Graphical abstractThe immunopathological niche in fibrosis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/694415v3_ufig1.gif" ALT="Figure 1000"> View larger version (47K): org.highwire.dtl.DTLVardef@122a24org.highwire.dtl.DTLVardef@8ca28borg.highwire.dtl.DTLVardef@103907borg.highwire.dtl.DTLVardef@10280e3_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsAdaptive and innate immune cells localize to the human MASH fibrotic niche CD8 T cells increase with MASH severity while MHC-II+ cells accumulate with fibrosis CXCR6+FASLG+ CD8 auto-aggressive T cells accumulate at the scar CXCL16+ scar-associated macrophages retain CD8 T cells in the fibrotic MASH niche Liver injury, inflammation and fibrosis persist in the absence of conventional T cells Impact and implicationsMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease in which fibrosis is a key determinant of patient outcomes and survival. This study demonstrates that fibrosis in MASH can develop independent of conventional T cell immunity, driven by myeloid cells including scar-associated macrophages (SAMs) and neutrophils within a localized hepatic niche in mice and humans. This highlights the need to prioritize innate immune mechanisms as key drivers of chronic (late-stage) liver disease for researchers and clinicians developing anti-fibrotic therapies.

immunology↗
bioRxiv2025

Shape-Dependent Toxicity of Gold Nanoparticles in Microalgae: Distinct Cellular and Molecular Responses

The ecotoxicological effects of engineered nanoparticles in aquatic environments are influenced not only by composition and size but also by particle morphology, yet shape dependent interactions with primary producers, remain poorly understood. In this study, we evaluated the cellular and molecular responses of freshwater algae (Chlamydomonas reinhardtii) following exposure to 100 nm silica-coated gold nanospheres (AuNP) and nanostars (AuNS) across multiple concentrations. Exposure to 10 mg/L AuNS for 72 h results in significantly stronger inhibition of algal growth and photosynthetic activity compared to the same concentration of AuNP. Morphometric profiling reveals that AuNS induced pronounced structural injury, including cell enlargement, debris production, and disruption of subcellular organization than AuNP. Confocal imaging suggested this heightened toxicity may stem from distinct internalization patterns, with AuNP primarily adhering to chloroplast surfaces, whereas AuNS penetrated more deeply into intracellular compartments. RNA sequencing identified 9 upregulated and 38 downregulated differentially expressed genes (DEGs) in the 10 mg/L AuNP treated cells, impairing photosynthesis and energy storage via the photosystem II subunit S1 (PSBS1)/ early light-inducible protein (ELI3) pathway. In contrast, the AuNS group exhibits 246 upregulated and 145 downregulated DEGs, affecting membrane integrity and nitrogen metabolism through the nitrate reductase (NIT1)/ aminomethyl transferase (AMT1)/ protein kinase domain-containing protein (A0A2K3CRU5) pathway. These results demonstrate that nanoparticle morphology can drive divergent toxicity mechanisms in algal cells. Our findings highlight the necessity of incorporating NPs morphology into environmental risk assessments and suggest that safer nanomaterial design should consider shape-dependent interactions with aquatic microorganisms. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/694526v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@29fbccorg.highwire.dtl.DTLVardef@5221a7org.highwire.dtl.DTLVardef@1f6249org.highwire.dtl.DTLVardef@6dc054_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗
bioRxiv2025

DOMINO: diffusion-optimised graph learning identifies domain structures with enhanced accuracy and scalability

Spatial transcriptomics enables in situ molecular profiling, allowing to measure the cellular transcriptional output within the tissue. As the tissue architecture is conserved, spatial domains with specific transcriptional patterns can be identified, facilitating the discovery and understanding of functional tissue compartments. Thus, several methods to uncover and identify these spatial domains have been developed. However, most of these existing methods do not scale to rapidly increasing data sizes and focus only on local structure while missing the global view of the tissue. Here, we present DOMINO, a diffusion-optimised contrastive learning framework for spatial domain detection. DOMINO utilises graph diffusion convolution to propagate information beyond immediate neighbours and jointly optimises local and, importantly, global graph structure via contrastive learning. This novel framework yields biologically interpretable domains with clearer boundaries and scales to large datasets, outperforming state-of-the-art methods across healthy and malignant benchmark datasets. We apply DOMINO to a newly generated spatial transcriptomic dataset of endometriosis-associated ovarian cancers, which could not be processed by existing domain detection methods owing to its size. We uncovered conserved proliferative and non-proliferative tumour states that recurred across these tumours and were independently validated in an external clear cell ovarian cancer spatial transcriptomic dataset. Proliferative domains were characterised by elevated expression of EIF4A1 and HSPA8, increased cell cycle activity, reduced mast cell abundance, and coordinated stromal remodelling, including altered fibroblast states and spatial organisation. In parallel, integrative analysis across tumours revealed subtype-specific multicellular ecosystems associated with either endometrioid or clear cell ovarian carcinomas, together with a tumour-excluded stromal domain that could only be resolved through the integration of spatial and transcriptional information. These findings demonstrate how well DOMINO scales up and that it uncovers biologically meaningful spatial programs spanning tumour intrinsic states, tumour microenvironment interactions, and subtype-specific tissue architecture that are not recovered by conventional expression-based clustering approaches.

bioinformatics↗
bioRxiv2025

Supplementation with a Limosilactobacillus fermentum K73 synbiotic modulates gut microbiota function and behavior in gnotobiotic mice transplanted with microbiota from children diagnosed with autism spectrum disorder

BackgroundGut dysbiosis has been implicated in numerous pathological conditions, including neurodevelopmental and neurodegenerative disorders. Recently, dietary interventions targeted at restoring microbial balance have therefore gained attention as potential therapeutic strategies. We recently demonstrated that an encapsulated synbiotic containing high-oleic palm oil and Limosilactobacillus fermentum K73 can modulate the metabolic activity and composition of human-derived gut microbiota in an in vitro batch bioreactor. Here, we extended this work through an in vivo supplementation pilot study using gnotobiotic mice colonized with gut microbiota from Colombian pediatric patients diagnosed with autism spectrum disorder (ASD) or age-matched neurotypical (NT) donors. Behavioral assessments and analyses of gut microbiota composition and function were performed before and after synbiotic supplementation. ResultsFirst, we found that the gut microbiota from Colombian ASD patients exhibited significantly reduced richness relative to NT donors, consistent with reports from other geographical regions, and displayed distinct compositional features unique to this population. Humanization of the gnotobiotic mice with this donor microbiota was successful, with murine gut communities reflecting features of their corresponding donor microbiota. Notably, synbiotic supplementation induced significant increases in the abundance of beneficial taxa and the production of short chain fatty acids that were more pronounced in mice colonized with ASD-derived microbiota, with concurrent behavioral changes associated with beneficial modulation of gut microbiota. ConclusionsOverall, we provide evidence that supports synbiotic supplementation as a viable strategy to positively modulate gut microbiome in conditions of dysbiosis. Our study also expands the body of knowledge of gut microbiome to understudied populations such as Latin America.

microbiology↗
bioRxiv2025

Molecular Surveillance Identifies Evidence of Getah Virus (GETV) in Mosquito Vectors in Alabama, USA

The Getah virus (GETV) is a mosquito-borne RNA virus in the Togaviridae family and the Alphavirus genus, associated with severe disease outbreaks in livestock across Asia-Pacific regions. Since its first isolation in Malaysia in 1955, GETV has been reported in Eurasia and the South Pacific, yet documented cases in the United States remain exceptionally rare, leaving major gaps in regional vector competence and surveillance data. To evaluate the potential of local mosquito populations as GETV carriers, field collections were conducted in Montgomery and Pike Road neighborhoods of Alabama from 2023 to 2024, capturing multiple mosquito species for molecular screening. Initial real-time qPCR assays on 200 pooled and individual samples suggested that approximate 30% of specimens demonstrated possible GETV carriage potential. To validate viral presence, two distinct primer sets were designed to amplify viral genome fragments. Mosquito RNA was reverse-transcribed into cDNA, followed by conventional PCR. The first PCR, targeting [~]280 bp, produced single or multiple amplicon bands in 32% of samples via gel electrophoresis. These positive cDNAs were re-amplified with a second primer pair targeting a [~]430 bp fragment from a separate genomic region, yielding confirmatory bands in 30% of specimens. Amplified products were purified and Sanger sequenced, revealing approximate 95% nucleotide similarity to the wild-type GETV reference genome. This study delivers the first field-based molecular evidence supporting GETV detection in Alabama mosquitoes, signaling either localized emergence or potential introduction of the virus. These findings underscore the need for expanded vector competence profiling, arboviral surveillance, and livestock disease preparedness in the southeastern United States, strengthening both public health readiness and state-level vector monitoring strategies.

microbiology↗
bioRxiv2025

Tau interactions with inner nuclear envelope proteins modulates chromatin

Abstract/SummaryThe intracellular re-distribution of the neuronal microtubule-associated protein Tau, from the axon into the somatodendritic compartment, is a physiological stress-related event and occurs early in Alzheimers disease (AD). Nuclear envelope distortions have been linked to the presence and aggregation of pathological Tau near the nucleus in these diseases. How physiologically increased soma Tau levels, enabling Tau interactions with the nucleus, impact nuclear integrity and neuronal physiology is unclear. Combining proximity biotinylation interactomics with chromatin imaging and molecular assays, we show that soluble Tau interacts with proteins coordinating chromatin at the inner nuclear membrane, including lamin B receptor and SUN1. This interaction promotes nuclear envelope invaginations and damage and changes the coordination of DNA at the nuclear lamina. Increasing somatodendritic Tau is sufficient to upregulate the expression of multiple transcription factors implicated in AD pathogenesis and to reduce expression of genes involved in cholesterol biosynthesis, which seem coordinated at lamin associated domains. These nuclear envelope-related mechanisms suggest that physiological, neuronal stress-related somatodendritic Tau missorting can initiate chromatin-related cascades important for early changes in AD and tauopathies.

neuroscience↗
bioRxiv2025

Dynamic alterations of DNA methylation and transcriptome in adaptation to and recovery from the space environment

Space exploration presents tremendous health challenges. Here, we report time series of multi-omic and phenotypic profiles of seventeen astronauts from six China Manned Space missions with continuous spaceflight durations ranging from 13 to 180 days. We revealed a key role of DNA methylation regulation in reshaping gene expression patterns to adapt to the space environment. Long-duration spaceflight showed more alterations in epigenetic modifications correlated with alternative splicing and protein acetylation. During recovery, an "overrange rebound" phenomenon was observed, furthermore, a mathematical model was established to describe this implying important phenomenon. Moreover, we revealed the correlations between molecular alterations and phenotypic changes such as coagulation activation and bone intensity loss. Additionally, we performed ground-based simulation experiments to estimate the impacts of individual stressors in the space environment on DNA methylation. In summary, our study highlights the importance and complexity of epigenetic regulation in adaptation to and recovery from the space environment.

genomics↗
bioRxiv2025

Antibacterial Activity of the Natural Product Elaiophylin against Streptococcus suis and its Biofilm Eradication Effect

The multidrug resistance (MDR) problem in Streptococcus suis(S. suis) is becoming increasingly severe, necessitating the development of novel antibacterial agents and strategies. In this study, seven Elaiophylin derivatives were isolated from Streptomyces sp. WS-30248, and the antibacterial activity and mechanism of action of the principal compound, Elaiophylin, against S. suis were systematically evaluated for the first time. Through comprehensive approaches including in vitro efficacy assays, biofilm inhibition and eradication tests, bacterial membrane integrity analysis, reactive oxygen species (ROS) level detection, and a mouse infection model, Elaiophylin was found to exhibit significant antibacterial activity against multiple clinically MDR S. suis strains. Its minimum inhibitory concentration (MIC) was as low as 0.5 g/mL, and complete bactericidal activity was achieved within 24 hours at 4xMIC. The compound effectively inhibited and eradicated bacterial biofilms, directly killing embedded cells within the biofilm matrix. Mechanistic studies revealed that Elaiophylin functions through multiple synergistic pathways, including disruption of bacterial membrane integrity and induction of massive ROS accumulation, thereby interfering with the proton motive force (PMF), depleting intracellular ATP, and blocking energy metabolism. In the mouse infection model, the Elaiophylin-treated group showed a significantly increased survival rate of 60% and effectively reduced bacterial loads in tissues. This study demonstrates that Elaiophylin is a highly promising natural candidate drug with multi-target synergistic effects, offering a new strategy to combat MDR S. suis and biofilm-associated infections.

microbiology↗
bioRxiv2025

Graded Notch Signaling Functions as a Rheostat of Lineage Plasticity and Therapy Resistance in Prostate Cancer

Resistance to androgen receptor (AR)-targeted therapies such as enzalutamide in castration-resistant prostate cancer (CRPC) often arises through lineage plasticity, yet the molecular mechanisms that define this process remain incompletely understood. While previous studies reported that Notch1 and Notch2 exert distinct and sometimes opposing effects in prostate cancer differentiation, the integrated role of Notch pathway activity has not been systematically explored. Here, we identify Notch signaling as a graded Rheostat that governs prostate cancer cell fate transitions. Integrative transcriptomic and functional analyses revealed that intermediate Notch activity maintains a stem-like progenitor state, whereas reduced or elevated signaling drives divergent differentiation trajectories toward luminal or neuroendocrine lineages, respectively. During CRPC progression and enzalutamide resistance, Notch signaling becomes dynamically rewired, peaking in progenitor-like populations that sustain plasticity and survival. Both CRISPR-mediated knockout and pharmacologic inhibition of Notch signaling depleted these progenitor cells and restored enzalutamide sensitivity. These findings demonstrate that the level, rather than the binary presence, of Notch signaling dictates lineage directionality and therapeutic response in CRPC, establishing it as a tunable and actionable driver of resistance.

cancer biology↗
bioRxiv2025

Microbial metabolism of complex organic matter across diverse deep-sea ecosystems

The deep sea is home to a vast and largely unexplored microbial biosphere, along with significant amounts of complex organic matter (COM). However, the ability of deep-sea microbes to metabolize complex organic matter across diverse regions remains poorly understood. Here, we combine 16S rRNA gene amplicon sequencing, metagenomics, and metatranscriptomics to comprehensively characterize prokaryotic communities across different years and habitats (cold seeps, hydrothermal vents, and seamounts). Our results reveal spatio-temporal community heterogeneity driven by geochemical gradients, alongside widespread genomic and transcriptomic potential for COM metabolism. Notably, the PVC (Planctomycetota-Verrucomicrobiota-Chlamydiota) superphylum exhibits extensive polysaccharide degradation capabilities, with Planctomycetota strain WC338 and Lentisphaerota strain WC36 isolated via laminarin enrichment. Growth and transcriptome data confirm their obligate laminarin dependence and robust degradation capacity, employing distinct enzymes (GH16 and GH2), whose broad distribution across diverse PVC superphylum lineages underscores their prevalence. Furthermore, we demonstrate that laminarin acts as a highly effective selective substrate for enriching and isolating the deep-sea PVC superphylum bacteria. Collectively, these findings delineate specialized adaptations within the PVC superphylum for polysaccharide degradation, significantly expanding our understanding of deep-sea microbial roles in global carbon cycling.

microbiology↗
bioRxiv2025

Structural basis for BCL7B-mediated ncBAF-nucleosome engagement

The mammalian SWI/SNF family of chromatin remodelers comprises BRG1/BRM-associated factor (cBAF), Polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF) complexes, which slide and disassemble nucleosomes to regulate gene expression and chromatin structure dependent on ATP hydrolysis energy. While the chromatin engagement mechanisms of cBAF and PBAF have been structurally resolved, the molecular architecture governing ncBAF interaction with chromatin remains elusive. In this study, by integrating cryo-electron microscopy, biochemical assays and cross-linking mass spectrometry, we resolved the conformational transition of ncBAF-nucleosome complexes from nucleotide-free to nucleotide-bound states. Our analyses establish BCL7 proteins as dynamic molecular tethers connecting the ARP module to the nucleosomal acidic patch and demonstrate that BCL7B promotes ncBAF-mediated nucleosome remodeling, with BRG1-catalyzed ATP hydrolysis triggering conformational changes that modulate BCL7-mediated histone association. Structurally and biochemically, we further demonstrate that {beta}-actin within the BCL7-containing ARP module retains ATP hydrolysis activity, rendering its exposed pointed end structurally compatible with incorporation into the barbed end of nuclear actin filaments, which provides a potential molecular basis for coordinating nuclear actin networks with chromatin remodeling. Collectively, our findings unravel a dynamic role of BCL7 in regulating ncBAF-mediated chromatin remodeling and establish a distinct chromatin engagement mode of ncBAF from that of cBAF/PBAF.

molecular biology↗