Biology subjects

Yang, N.

Publications and source records attributed to Yang, N..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Central carbon metabolism switching in lytic versus temperate coral reef viral communities

Coral reefs are declining globally due in part to bacterial overgrowth, a process known as microbialization. However, the role of bacteriophages that may inhibit microbialization by infecting and killing these bacteria remains poorly understood, especially their metabolic impacts on bacterial proliferation. To address this, we analyzed central carbon metabolism gene frequencies in viral communities from healthy (lytic-dominated) and degraded (temperate-dominated) Central Pacific coral reefs. We found that viral metabolism shifted broadly from being dominated by metabolism that builds up pools of central intermediates on degraded reefs dominated by temperate viral infection ("anaplerotic" reactions) to metabolism that consumes these pools to prioritize production of metabolic precursors for virion construction on healthy reefs dominated by lytic infection ("cataplerotic" reactions). This switch was shown by the over-representation of Entner-Doudoroff (ED) glycolysis genes on degraded, temperate-dominated reefs and of pentose phosphate pathway (PPP) and reductive tricarboxylic acid cycle (TCA) genes on healthy, lytic-dominated reefs. As a result of this metabolic dichotomy, our qualitative compartment modeling revealed two distinct ecosystem states: (i) healthy reefs, where lytic viral metabolism enhances viral production and suppresses bacterial overgrowth, and (ii) degraded reefs, where temperate viral metabolism accelerates bacterial proliferation. Because viral switching between lytic and temperate lifestyles is a known function of host physiological state, these findings position viral metabolism as both a driver of reef decline and a conservation lever, with metabolically mediated "re-viralization" offering a novel strategy to restore reef resilience.

ecology↗

bioRxiv2025

Uterine immune dysregulation after asynchronous transfer induced embryonic apoptosis in mice

Asynchronous embryo transfer is widely used in assisted reproduction, yet its adverse effects and mechanisms remain unclear. This study investigates implantation failure in D1.5 pseudopregnant mice to elucidate mechanisms underlying asynchronous transfer. Blastocysts were transferred into uterine horns of D1.5 (Group A), D2.5 (Group B), and D3.5 (Group C) recipients. Implantation sites were counted at D7.5, and embryos were recovered within 3 hours post-transfer for analysis. Multibarcode single-cell RNA sequencing was applied to embryos and uterine tissues. Embryo recovery rate in Group A was significantly lower than in Groups B and C (p<0.01), with an abnormal embryo rate of 68.67%. Hoechst 33342/PI double staining revealed dead-cell features in abnormal embryos. Transcriptomic analysis of embryos showed downregulated DNA damage repair and structural maintenance genes in Group A. GO and KEGG analyses highlighted enrichment in transcriptional regulation and cell cycle pathways. GSEA identified activated apoptosis pathways, with intrinsic (mitochondrial) and extrinsic (death receptor TNFR-mediated) apoptosis genes significantly upregulated (p<0.05). Uterine transcriptome analysis revealed downregulated collagen family genes (ECM maintenance) but upregulated immune-related genes (IL family, CDs, C3) in Group A. Functional enrichment confirmed ECM and immune regulation pathway involvement. Gene network analysis identified Clca1, Smpdl3a, Tmprss4, Muc4, Cfb, and Nupr1 as key regulators of D1.5 uterine immunity/inflammation. D1.5 uterine immune dysregulation induces embryonic stress and inflammation. Impaired DNA damage repair activates intrinsic apoptosis, while upregulated TNFR signaling triggers extrinsic apoptosis, collectively blocking embryonic development toward implantation competence. These findings provide mechanistic insights into optimizing embryo transfer timing and improving reproductive outcomes.

immunology↗

bioRxiv2025

Asymmetric Social Representations in the Prefrontal Cortex for Cooperative Behavior

Cooperation is a hallmark of social species, enabling individuals to achieve goals that are unattainable alone. Across species, cooperative behaviors are often organized by distinct social roles such as leaders and followers, yet the neural mechanisms supporting such role-based coordination remain elusive. Here we introduce a new paradigm for studying cooperation in mice, where pairs of animals engage in a joint spatial foraging task that naturally gives rise to stable leader-follower roles predictive of learning speed. Disruption of medial prefrontal cortex (mPFC) activity, particularly in followers, impairs cooperation and induces reciprocal shifts in how animals weigh self- and partner-related cues for decision-making. Calcium imaging reveals that mPFC encodes both leadership dynamics and an egocentric social value map of the partners position, each in an asymmetric, role-specific manner. Combining this behavior with a novel multi-agent inverse reinforcement learning framework, we identify latent value functions that guide cooperative decisions and are decodable from mPFC activity. These findings uncover fundamental neural computations that support cooperation, revealing how social roles shape decision-making in real time. Our work opens new avenues for investigating the cellular and circuit basis of social cognition and collective behavior.

neuroscience↗

bioRxiv2025

Comparative proteomic analysis of the ECM composition of the human omentum and mesentery, the main sites of ovarian cancer metastasis

Due to its limited symptoms, high-grade serous ovarian cancer (HGSOC) has frequently metastasized extensively throughout the peritoneal cavity prior to its diagnosis, resulting in an overall five-year survival rate of less than 50%. The greater omentum and the small bowel mesentery are two of the most common metastatic sites in advanced HGSOC. However, the mechanisms underlying HGSOC metastatic tropism remain unknown. The extracellular matrix is a complex and dynamic meshwork of proteins that provides biochemical and mechanical signals to surrounding cells and has been shown to drive the dissemination of several cancer types to preferential distant sites. Here, using histological assessment and proteomics, we examined the composition of the extracellular matrix of paired omentum and mesentery samples from disease-free adult females. We found that the fibrillar collagen content of the mesothelial layer of the omentum was significantly higher than that of the mesentery. Using ECM-focused proteomics, we further defined the ECM composition - or matrisome - of these two tissues. We found that over 90% of the proteins detected were shared between the omentum and mesentery. Our analysis also revealed small subsets of tissue-specific ECM proteins. Future work will aim to test the possible functional contributions of these ECM proteins to HGSOC metastatic tropism. To facilitate the reuse of our dataset, we have deposited the raw mass spectrometry data and accompanying metadata files to the ProteomeXchange Consortium with the dataset identifier PXD061586.

cancer biology↗

bioRxiv2025

Cell-specific RNA isoform remodeling in the aging mouse brain

Aging is associated with increases in risk of multiple chronic diseases and at the cellular level, with disruptions in RNA homeostasis. Single-cell transcriptomic studies have revealed RNA abundance heterogeneity across brain cell types but the more complex changes in RNA processing such as alternative splicing, isoform usage, transcription start and polyadenylation site selection remain uncharacterized. Here, we combine single-cell analysis with long-read nanopore sequencing to capture full-length RNA isoforms and uncover temporal changes in RNA transcription, processing, and alternative splicing in the aging mouse cortex and hippocampus. By profiling transcriptomes from young adult to very old mice, we identify non-linear, cell-type-specific isoform expression changes and isoform usage shifts, primarily driven by transcription start site selection. These aging-associated isoform changes alter the coding potential and poly(A) site position of genes. Our data also reveal a high proportion of senescence in immune cells, far exceeding that of other cell types. We also identify isoform markers that, when applied to a machine learning model, distinguish senescent from normal immune cells. This study provides a full-length RNA isoform-based atlas of the aging mouse brain, offering insights into RNA metabolism remodeling across brain cell types throughout the lifespan.

genomics↗

bioRxiv2025

TypeSINE: Genome-Wide Detection of SINE Retrotransposon Polymorphisms Reveals Functional Variants Linked to Body Size Variation in Pigs

The genotyping of Short Interspersed Element (SINE) retrotransposon insertion polymorphisms (RIPs) from large-scale sequencing data remains technically challenging. To overcome this limitation, we developed TypeSINE to genotype SINE-RIPs from short-read sequencing data. Analyzing 362 porcine genomes, we identified 749,835 SINE-RIPs (>85% accuracy), including 65,917 common variants (5-95% frequency). These showed uniform genomic distribution ([~]22/Mb), with 40% in introns. Population analyses based on SINE-RIPs revealed independent domestication of Asian and European pigs from local wild populations, followed by introgression. GWAS detected body size-associated regions using SINE-RIPs. We created pigRIPdb (82,227 curated SINE-RIPs) with browsing and visualization tools. The methods cross-species applicability is supported by conserved SINE evolutionary patterns, enabling polymorphism discovery of SINEs in livestock and humans. TypeSINE represents an efficient, scalable solution for genome-wide SINE-RIP analysis, advancing population genomics research. TeaserAn integrated SINE-RIP genotyping platform with companion database enables large-scale analysis of SINE evolution and population genetics in swine

bioinformatics↗

bioRxiv2025

Fibronectin Composition and Transglutaminase 2 Cross-linking Cooperatively Regulate Ovarian Cancer Cell Adhesion in ECM-Mimetic Constructs

The extracellular matrix (ECM) plays a crucial role in tumor progression. Here, we analyzed collagen I and cellular fibronectin (cFN) in normal omentum and metastatic omentum from high-grade serous ovarian cancer (HGSOC). The levels of both proteins were significantly elevated and collagen I fibers were significantly thicker in HGSOC metastases. Moreover, the ECM cross-linking enzyme transglutaminase 2 (TG2) was increased in omental metastases, where it is enzymatically active in the extracellular environment. This information was used to develop ECM constructs recapitulating these key changes, alone and in combination, to investigate their impact on HGSOC cell adhesion. To our knowledge, this is the first report using TG2 as a cross-linking agent to generate constructs from multiple ECM components. Low levels of HGSOC cell adhesion were observed on colIagen-only (coll) gels, while inclusion of cFN or plasma fibronection (pFN) increased cell adhesion. TG2-mediated cross-linking of colI/cFN hydrogels promoted HGSOC cell adhesion, while cross-linking of coll/pFN had no effect. Cell adhesion was dependent on ligand identity and fiber diameter. When fiber thickness was held constant, the inclusion of cFN led to greater HGSOC cell adhesion relative to pFN or coll, due to interactions of {beta}1 integrins with the EDA and RGD domains of cFN. Meanwhile, when gel composition was held constant, HGSOC cell adhesion increased as fiber thickness was increased through modifications to gelation temperature. Combined, our results demonstrate how ECM changes associated with omental metastasis can support tumor progression and provide insights into methods to tailor biomaterials to support cell adhesion.

bioengineering↗

bioRxiv2025

Eukaryotic biodiversity and ecological networks from the surface to the mesopelagic in the Northwest Atlantic Slope Water

1.The diversity and interactions among mesopelagic organisms are difficult to study and as a result, are insufficiently unaccounted for in food web and biogeochemical models. This knowledge gap hinders our ability to model and forecast ecosystem function and formulate effective policies for conservation and management in the face of growing interest in exploiting midwater living resources. We used multi-marker metabarcoding of environmental DNA (eDNA) samples collected from Northwest Atlantic Slope Water to resolve patterns of eukaryotic community composition spanning taxonomically across protists (microbial eukaryotes), invertebrates, and vertebrates and vertically from the ocean surface to the base of the mesopelagic zone. With statistical network analyses, we explored cross-kingdom associations including putative trophic dynamics such as food web interactions and evaluated network robustness to biodiversity loss. We found depth-specific communities of distinct protist, invertebrate, and vertebrate assemblages. Ecological networks for the epipelagic, upper mesopelagic, and lower mesopelagic suggest that protists are keystone taxa and important mediators of trophic interactions; they increase network complexity and contribute to network stability. We also identified metazoans including copepods, gelatinous taxa (cnidarians, tunicates), and mesopelagic fish as important components of network interactions. Our study demonstrates a holistic approach to generate insights on mesopelagic biodiversity and implications for ecosystem resilience that can inform ocean governance.

ecology↗

bioRxiv2025

Varigraph: an accurate and widely applicable pangenome graph-based variant genotyper for diploid and polyploid genomes

Graph pangenome references can address single-reference bias, thereby enhancing the accuracy of variant genotyping and empowering downstream applications in population genetics and quantitative genetics. However, existing pangenome-based genotyping methods struggle with large or complex pangenome graphs, particularly in polyploid genomes. Here, we introduce Varigraph, an algorithm that leverages the comparison of unique and repetitive k-mers between variant sites and short reads for genotyping both small and large variants. Varigraph outperforms current state-of-the-art linear and graph-based genotypers across non-human genomes while maintaining comparable accuracy in human genomes. By employing an efficient data structure, Varigraph achieves higher accuracy in repetitive regions while managing computational costs for large datasets. Notably, Varigraph is the first tool capable of effectively utilizing pangenome graphs for genotyping autopolyploids, enabling precise determination of allele dosage. This work provides a robust and accurate solution for genotyping non-human genomes and will facilitate genomic studies of polyploid crops.

genomics↗

bioRxiv2025

Pooled screening identifies combinatorial CAR signaling domains for next-generation CAR-M immunotherapies

Chimeric antigen receptor-engineered macrophages (CAR-Ms) hold great promise for solid tumor immunotherapy. The intracellular domains (ICDs) of CARs determine the phenotypic output of therapeutic macrophages but remain largely unexplored. Here, we constructed a CAR library containing 131 unique signaling domains derived from native immune receptors and identified 17 ICDs that enhance macrophage phagocytosis, inflammatory responses, or tumor infiltration in vitro and in vivo. We further developed a scalable 3 barcode technology, CARode, to uniquely label and trace ICD variants within large-scale combinatorial CAR library and applied it to single-cell RNA sequencing and single-cell CAR analysis to assess the synergetic effects of ICD combinations on macrophage activation. Our approach uncovered a novel CD40-LY9-FCRL1 chimeric receptor that modulates the tumor microenvironment and improves solid tumor clearance. In conclusion, our findings demonstrate that pooled screening can accelerate the discovery of complex ICD constructs, providing a powerful platform for engineering macrophage-based immunotherapies.

bioengineering↗

bioRxiv2025

Isostere 18F-protein post-translational editing enables dynamic tracking of neurodegeneration biomarkers

The neurofilament light chain protein (NfL) is a suggested general marker for neuronal loss. Its release from brain parenchyma into cerebral spinal fluid, and presumed detection in blood has seen it established as a first blood-based marker of disease activity and drug efficacy in multiple sclerosis (MS) and in the presymptomatic diagnosis and assessment of disease course for other neurodegenerative disorders.1 However, the lack of characterisation of its behaviour in circulation, largely due to its antibody-dependent measurement, have hampered the biological interpretation of these measurements, especially after acute injury such as in MS relapse or head trauma.2 Here, we describe a strategy for exploiting positron emission tomography (PET) imaging using isosteric protein mimics following the installation of a fluorine-18 label that is benign enough to provide sensitive, real-time information on the dynamics and trafficking of NfL protein. This circumvents the limits of current methods that integrate 18F into proteins through the bio-conjugation of bulky, unnatural groups, which we show perturb NfLs assembly and functional properties from those in the natural state. We use a visible-light-driven reaction to access radioactive isostere proteins that are unperturbed and so closely resemble their native form. In this way, generation of [18F]fluoroalkyl radicals that can be rapidly reacted at pre-defined sites on proteins creates mimics of proteinogenic side chains bearing near-zero-size labels to probe proteins in functionally true form. These prosthetic-free, protein radiotracers can be generated in excellent radiochemical yield (up to 67%) via a semi-automated protocol in just 15 mins. High associated molar activities (precursor up to 102 GBq mol-1) allowed high sensitivity dynamic observations in blood, brain and cerebrospinal fluid, enabling even the first unambiguous observations of spinal flow kinetics using proteins. These dynamics, including the high rate of spinal flow (on the order of mm per min) and drainage of NfL from CSF into sacral lymph nodes, now provides evidence that the slow fall rate of antibody-detected markers that is observed after acute neural insults is not due to a long half-life, but rather reflects sustained neuronal loss. This discovery will now help to better correlate clinical and radiological features of disease with NfL blood levels. Our methodology now demonstrates the broad potential of a near-zero-size labelling method for the functional study of proteins in whole organisms without interfering with their biological activity and native assembly.

synthetic biology↗

bioRxiv2024

Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission

Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder (BD) and schizophrenia (SCZ), implicating a shared disease mechanism driven by loss-of-function. AKAP11, a protein kinase A (PKA) adaptor, plays a key role in degrading the PKA-RI complex through selective autophagy. However, the neuronal functions of AKAP11 and the impact of its loss-of-function remains largely uncharacterized. Through multi-omics approaches, cell biology, and electrophysiology analysis in mouse models and human induced neurons, we delineated a central role of AKAP11 in coupling PKA kinase network regulation to synaptic transmission. Loss of AKAP11 distorted compartment-specific PKA and GSK3/{beta} activities and impaired cellular functions that significantly overlap with pathways associated with BD and SCZ. Moreover, we identified interactions between AKAP11, the PKA-RI adaptor SPHKAP, and the ER-resident autophagy-related proteins VAPA/B, which co-adapt and mediate PKA-RI complex degradation in neurons. Notably, AKAP11 deficiency impaired neurotransmission, providing key insights into the mechanism underlying AKAP11-associated psychiatric diseases.

neuroscience↗

bioRxiv2024

Expanding GABAergic Neuronal Diversity in iPSC-Derived Disease Models

GABAergic interneurons comprise diverse molecular and functional subtypes that contribute to neural circuit assembly and are implicated in a range of neurodevelopmental and neuropsychiatric disorders. Traditional approaches for differentiating human pluripotent stem cells (PSCs) into neurons often face challenges such as incomplete neural differentiation, prolonged culture periods, and variability across PSC lines, which can constrain their application in disease modeling. To address these limitations, we developed a strategy that combines inducible expression of the transcription factors (TFs) ASCL1 and DLX2 with dual-SMAD and WNT inhibition to efficiently drive differentiation of human PSCs into diverse, region-specific GABAergic neuronal types. Using single-cell sequencing, we characterized the cellular heterogeneity of GABAergic induced neurons (iNs) generated with the patterning factors (patterned iNs) and those derived solely with TFs (PSC-derived iNs), revealing distinct interneuron subtype compositions and the regulatory programs that govern their fate specification. Patterned iNs exhibited gene expression features corresponding to multiple brain regions, particularly the ganglionic eminence (GE) and neocortex, whereas GABAergic PSC-derived iNs predominantly resembled hypothalamic and thalamic neurons. Both iN types were enriched for genes relevant to neurodevelopmental and psychiatric disorders, with patterned iNs more specifically linked to neural lineage genes, highlighting their utility for disease modeling. We further applied this protocol to investigate the impact of a recurrent ADNP syndrome-associated mutation (p.Tyr719*) on GABAergic neuron differentiation, revealing that this mutation disrupts GABAergic fate specification and synaptic transmission. Overall, this study expands the toolkit for disease modeling by demonstrating the complementary advantages of GABAergic PSC-derived iNs and patterned iNs in representing distinct GABAergic neuron subtypes, brain regions, and disease contexts. Together, these approaches provide a flexible platform for investigating molecular and cellular mechanisms relevant to neurodevelopmental and neuropsychiatric disorders.

developmental biology↗

bioRxiv2024

Functional, Biotinylproteomic and Bioinformatic Analysis of Both Cytoskeletal and Plastoskeletal Proteins in Plant Mechanoresponse

To investigate the early signaling components of skeletal proteins in mediating Arabidopsis thigmomorphogenesis, both microscopic and proximity labeling (PL)-based quantitative biotinylproteomics were applied to investigate the subcellular location and putative interactors of a touch-responsive WPRa4 protein. These experiments have demonstrated that the cytoskeletal protein WPRa4 is localized nearby the plastid. Several cytosolic Plastid Movement-Impaired (PMI) proteins and a member of the plastidic translocon were identified as putative interactors of WPRa4, suggesting an integrated network of skeletal proteins linking the cytoskeleton with the plastid membrane. Further bioinformatic analysis of both Proximity Labeling- and XL-MS-based proteomic results suggested that Plastid Movement-Impaired 4 (PMI4) protein may serve as a candidate in mediating the plant touch response. The loss-of-function pmi4 mutant showed neither the touch-induced bolting delay nor the rosette size reduction upon repetitive touches, suggesting that pmi4 is a unique type of mutant of Arabidopsis thigmomorphogenesis. Moreover, the null mutant pmi4 displayed a severe defect in the touch-induced Ca2+ oscillation. Further transcriptomic analysis performed on both the wild-type Arabidopsis and pmi4 mutant indicated that the mutated pmi4 gene suppressed the expression of a number of touch rapidly induced transcripts and a JA-responsive gene, LOX2. These findings led us to propose a revised touch force-sensing theory, in which the interconnected cytosolic and plastidic skeletal proteins serve as the early mechano-sensing components mediating Arabidopsis thigmomorphogenesis and the retrograde calcium signaling in response to touch.

plant biology↗

bioRxiv2024

Berberine: A dual anti-HIV and anti- cervical cancer compound

We report the effects of berberine (BBR), a benzylisoquinoline alkaloid small molecule on inhibition of HIV infection of cervical cancer cells. We used HeLa cell-derived TZM-bl cell line as a model of cervical cancer and HIV infection. BBR significantly inhibits viral and cancer processes, including expression of cell-associated HIV RNA, secretion of HIV reverse transcriptase, and HIV Tat-mediated LTR promoter transactivation. BBR significantly inhibits HIV-induced cancer cell viability and cell clustering. Besides its ability to inhibit HIV-induced cancer cell viability, BBR inhibits migration and matrix invasion of cervical cancer cells that are infected with HIV or treated with HIV Tat protein. The ability of BBR to inhibit cell clustering, collective cell migration, and cell invasion may have an effect in controlling progression of cervical cancer and HIV since collective migration and invasion are strategies for local tissue infiltration, as well as metastatic invasion in epithelial cancers. Interestingly, molecular docking and dynamic stimulation show that BBR binds HIVIIIB Tat amino acid residues through non-covalent interactions that occurs at multiple sites including LYS71, providing mechanistic insights into BBR regulation HIV infection. The results of the present study suggest that BBR has the potential to inhibit HIV infection and comorbid cervical cancer progression. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/624212v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1b88635org.highwire.dtl.DTLVardef@17311d8org.highwire.dtl.DTLVardef@19881c7org.highwire.dtl.DTLVardef@170483a_HPS_FORMAT_FIGEXP M_FIG C_FIG Berberine (BBR), a benzylisoquinoline alkaloid small molecule, inhibits HIV infection of cervical cancer cells, suppresses HIV-induced migration and invasion of the cancer cells. Mechanistically, BBR interferes with Tat-mediated HIV LTR promoter transactivation and expression of different HIV RNA species, expression of early genes (multiply spliced Tat-Rev) and late genes (unspliced Gag-Pol).

molecular biology↗

bioRxiv2024

Loss of TMEM55B modulates lipid metabolism through dysregulated lipophagy and mitochondrial function

Lipophagy is a form of selective autophagy that targets the lipid droplets for lysosomal decay and has been implicated in the onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Factors that augment lipophagy have been identified as targets for MASLD therapeutic development. TMEM55B is a key regulator of lysosomal positioning which is critical for the lysosome fusion with the autophagosome, but less studied. Here, we demonstrate that inhibition of TMEM55B in murine models accelerates MASLD onset and progression. In cellular models, TMEM55B deficiency enhances lipophagy, leading to increased fatty acid release from lysosomes to mitochondria but simultaneously impairs mitophagy, causing an accumulation of dysfunctional mitochondria. This imbalance leads to increased lipid accumulation and oxidative stress, worsening MASLD. These findings underscore the importance of lysosomal positioning in lipid metabolism and suggest that augmenting lipophagy may exacerbate disease in the context of mitochondrial dysfunction.

cell biology↗

bioRxiv2024

Pan-cistrome analysis of the leaf accessible chromatin regions of 214 maize inbred lines

Characterizing the noncoding regions of the genome, particularly the cis-regulatory elements (CREs) located in accessible chromatin regions (ACRs) in gene promoters, is crucial for understanding how gene expression is regulated and how genotype contributes to phenotypic diversity in plants.In this study, we used ATAC-seq to resequence and map the ACRs of 214 maize inbred lines. We identified 82,174 ACRs and reported that 39.55% of them exhibited significant variation across the population. Next, we used the accessibility of ACRs as a quantitative feature and performed a chromatin associability GWAS (caGWAS), resulting in 27,004 caQTLs. Among them, 2,463 were predicted to disrupt the cis-regulatory elements that TF binds in these ACRs, suggesting that TF binding affects chromatin accessibility. Specifically, we identified two caACRs that regulate the expression of fad7, which encodes a fatty acid desaturase and affects the linolenic acid content.Our findings highlight the dynamic nature of maize ACRs and demonstrate that chromatin accessibility information could be used for GWASs, offering key insights into the genetic and regulatory mechanisms of chromatin accessibility and its impact on complex traits in plants.

genomics↗

bioRxiv2024

Loss of H3K9 trimethylation leads to premature aging

Aging is the major risk factor for most human diseases and represents a major socio-economical challenge for modern societies. Despite its importance, the process of aging remains poorly understood. Epigenetic dysregulation has been proposed as a key driver of the aging process. Modifications in transcriptional networks and chromatin structure might be central to age-related functional decline. A prevalent feature described during aging is the overall reduction in heterochromatin, specifically marked by the loss of repressive histone modification, Histone 3 lysine 9 trimethylation (H3K9me3). However, the role of H3K9me3 in aging, especially in mammals, remains unclear. Here we show using a novel mouse strain, (TKOc), carrying a triple knockout of three methyltransferases responsible for H3K9me3 deposition, that the inducible loss of H3K9me3 in adulthood results in premature aging. TKOc mice exhibit reduced lifespan, lower body weight, increased frailty index, multi-organ degeneration, transcriptional changes with significant upregulation of transposable elements, and accelerated epigenetic age. Our data strongly supports the concept that the loss of epigenetic information directly drives the aging process. These findings reveal the importance of epigenetic regulation in aging and suggest that interventions targeting epigenetic modifications could potentially slow down or reverse age-related decline. Understanding the molecular mechanisms underlying the process of aging will be crucial for developing novel therapeutic strategies that can delay the onset of age-associated diseases and preserve human health at old age specially in rapidly aging societies.

physiology↗