Biology subjects

Li, D.

Publications and source records attributed to Li, D..

At least 631 records · Page 35Linked to original sources

bioRxiv2019

Improving ATAC-seq Data Analysis with AIAP, a Quality Control and Integrative Analysis Package

ATAC-seq is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis. Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data; however, key quality control (QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics, including reads under peak ratio (RUPr), background (BG), promoter enrichment (ProEn), subsampling enrichment (SubEn), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package (AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity (20%~60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and with one command line execution, it generates a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed qATACViewer for the user-friendly interaction with the QC report.

bioinformatics↗

bioRxiv2019

Serum Amyloid A Proteins Induce Pathogenic TH17 Cells and Promote Inflammatory Disease

Lymphoid cells that produce IL-17 cytokines protect barrier tissues from pathogenic microbes, but are also prominent effectors of inflammation and autoimmune disease. T-helper (TH17) cells, defined by ROR{gamma}t-dependent production of IL-17A and IL-17F, exert homeostatic functions in the gut upon microbiota-directed differentiation from naive CD4+ T cells. In the non-pathogenic setting, their cytokine production is regulated by serum amyloid A proteins (SAA1 and SAA2) secreted by adjacent intestinal epithelial cells. However, TH17 cell behaviors vary markedly according to their environment. Here we show that SAAs additionally direct a pathogenic pro-inflammatory TH17 cell differentiation program, acting directly on T cells in collaboration with STAT3-activating cytokines. Using loss- and gain-of-function mouse models, we show that SAA1, SAA2, and SAA3 have distinct systemic and local functions in promoting TH17-mediated inflammatory diseases. These studies suggest that T cell signaling pathways modulated by the SAAs may be attractive targets for anti-inflammatory therapies.

immunology↗

bioRxiv2019

Antisense oligonucleotide therapy rescues aggresome formation in a novel Spinocerebellar Ataxia type 3 human embryonic stem cell line.

Spinocerebellar ataxia type 3 (SCA3) is a fatal, late-onset neurodegenerative disorder characterized by selective neuropathology in the brainstem, cerebellum, spinal cord, and substantia nigra. Here, we characterize the first NIH-approved human embryonic stem cell (hESC) line derived from an embryo harboring the SCA3 mutation. Referred here as SCA3-hESC, this line is heterozygous for the mutant polyglutamine-encoding CAG repeat expansion in the ATXN3 gene within the pathogenic repeat range for SCA3. We observed relevant molecular hallmarks of the human disease at all differentiation stages from stem cells to cortical neurons, including robust ATXN3 aggregation and altered expression of key components of the protein quality control machinery. Finally, antisense oligonucleotide-mediated reduction of ATXN3 prevented the formation of p62-positive aggresomes in SCA3-hESCs. The SCA3-hESC line offers a unique and highly relevant human disease model that holds strong potential to advance understanding of SCA3 disease mechanisms and facilitate the evaluation of possible SCA3 therapies.\n\nHighlightsO_LIGenerated first NIH-approved SCA3 human embryonic stem cell line (SCA3-hESC)\nC_LIO_LISCA3-hESC exhibit robust ATXN3 aggregation pathology and form p62+ aggresomes\nC_LIO_LIAnti-ATXN3 antisense oligonucleotides rescue aggresome formation in SCA3-hESC\nC_LIO_LIDerived SCA3 neurons form aggregates and exhibit impaired protein quality control\nC_LI

neuroscience↗

bioRxiv2019

Multimodal memory components and their long-term dynamics identified in cortical layers II/III but not layer Vb

Activity patterns of cerebral cortical regions represent the present environment in which animals receive multi-modal inputs. They are also shaped by the history of previous activity that reflects learned information on past multimodal exposures. We studied the long-term dynamics of cortical activity patterns during the formation of multimodal memories by analysing in vivo high-resolution 2-photon mouse brain imaging of Immediate Early Gene expression, resolved by cortical layers. Strikingly, in layers II/III, the patterns showed similar dynamics across functional distinct cortical areas and the consistency of dynamic patterns lasts for one to several days. In contrast, in layer Vb, the activity dynamics varied across functional distinct areas, and the present activities are sensitive to the previous activities at different time depending on the cortical locations, indicating that the information stored in the cortex at different time points is distributed across different cortical areas. These results suggest different roles of layer II/III and layer Vb neurons in the long-term multimodal perception of the environment.

neuroscience↗

bioRxiv2019

Efficient RNA-mediated reprogramming of human somatic cells to naive pluripotency facilitated by tankyrase inhibition

In contrast to conventional human pluripotent stem cells (hPSC) that are related to post-implantation embryo stages, naive hPSC exhibit features of pre-implantation epiblast. Naive hPSC are established by resetting conventional hPSC, or are derived from dissociated embryo inner cell masses. Here we investigate conditions for transgene-free reprogramming of human somatic cells to naive pluripotency. We find that tankyrase inhibition promotes RNA-mediated induction of naive pluripotency. We demonstrate application to independent human fibroblast cultures and endothelial progenitor cells. We show that induced naive hPSC can be clonally expanded with a diploid karyotype and undergo somatic lineage differentiation following formative transition. Induced naive hPSC lines exhibit distinctive surface marker, transcriptome, and methylome properties of naive epiblast identity. This system for efficient, facile, and reliable induction of transgene free naive hPSC offers a robust platform, both for delineation of human reprogramming trajectories and for evaluating the attributes of isogenic naive versus conventional hPSC.

developmental biology↗

bioRxiv2019

Verify Hub Genes of expression profile in aortic dissection

BackgroundTo assess the mRNAs expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD). Methodology: mRNA microarray expression signatures of TAD tissues (n=6) and no TAD tissues (NT;n=6) were analyzed by Arraystar human mRNAs microarray. Real-time PCR (qRT-PCR) were used to validate the result of mRNAs microarray. Bioinformatic tools including gene ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis were utilized. The protein-protein interaction networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytohubba analysis were used to infer the most hug gene and pathways. Results: The top 10 hub genes CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG,CXCL12 and ASPM were identified from the PPI network. Module analysis revealed that TAD was associated with cell cycle, oocyte meiosis, p53 signaling pathway, progesterone-mediated oocyte maturation. The qRT-PCR result showed that the expression of all hug genes was significantly increased in TAD samples (p < 0.05). Conclusions: These candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.\n\nAuthor summaryMany basic characteristics underlying the establishment of aortic dissection have not been studied in detail. The presented work sought to understand the pathogenesis of human thoracic aortic dissection by employing bioinformatic tools to explore the hub mRNAs and potential molecular mechanisms of thoracic aortic dissection. Many pathway were thought to have relevant with this disease, but the most important pathway was not define. We used bio-mathematical analysis to explore the potential functions in thoracic aortic dissection and identified the hub genes and explored the intrinsic molecular mechanisms involved in thoracic aortic dissection between two microarray analysis. Finally, we indentified the cell cycle maybe the key pathway in thoracic aortic dissection.

bioinformatics↗

bioRxiv2019

Cyclosporine A Directly Affects Human and Mouse B cell Migration in vitro by Disrupting a HIF-1α Dependent, O2 Sensing, Molecular Switch

BackgroundHypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1 post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1 destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality.\n\nResultsWe demonstrate that O2 tension is a previously unrecognized Bc regulatory switch, altering CXCR4 chemokine receptor signaling in activated Bc through HIF-1 expression and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this O2 regulatory switch in primary human Bc.\n\nConclusionThis previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.

immunology↗

bioRxiv2019

Exogenous Melatonin accelerates seed germination in cotton(Gossypium hirsutum L.)

Seed germination is considered as the beginning of the spermatophyte lifecycle, as it is a crucial stage in determining subsequent plant growth and development. Although many previous studies have found that melatonin can promote seed germination, the role of melatonin in cotton germination remains unexamined. The main objective of this study is the characterization of potential promotional effects of melatonin (at doses of 0, 10, 20, 50, 100 and 200 M) on cotton seed germination. This experiment demonstrated that low concentrations of melatonin can promote germination, while high concentrations failed to promote germination and even inhibited germination. Together, these results indicate that a 20 M melatonin treatment optimally promotes cotton seed germination. Compared with the control, germination potential (GP), germination rate (GR) and final fresh weight (FW) increased by 16.67%, 12.30% and 4.81% respectively. Although low concentrations of melatonin showed some improvement in vigor index (VI), germination index (GI) and mean germination time (MGT), these effects did not reach significant levels. Antioxidant enzyme activity during seed germination was most prominent under the 20 M melatonin treatment. Superoxide dismutase (SOD) and peroxidase (POD) activities were significantly increased by 10.37-59.73% and 17.79-47.68% compared to the melatonin-free control. Malondialdehyde (MDA) content was reduced by 16.73-40.33%. Two important plant hormones in seed germination were also studied. As melatonin concentration increased, ABA content in seeds decreased first and then increased, and GA3 content showed a diametrically opposite trend, in which the 20 M melatonin treatment was optimal. The 20 M melatonin treatment reduced ABA content in seeds by 42.13-51.68%, while the 20 M melatonin treatment increased GA3 content in seeds to about 1.7-2.5 times that of seeds germinated without melatonin. This study provides new evidence suggesting that low concentrations of melatonin can promote cotton seed germination by increasing the activity of antioxidant enzymes, thereby reducing the accumulation of MDA and regulating plant hormones. This has clear applications for improving the germination rate of cotton seeds using melatonin.

plant biology↗

bioRxiv2019

Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes

Germline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.

cancer biology↗

bioRxiv2019

High specificity of widely used phospho-tau antibodies validated using a quantitative whole-cell based assay

Antibodies raised against defined phosphorylation sites of the microtubule-associated protein tau are widely used in scientific research and being applied in clinical assays. However, recent studies have revealed an alarming degree of non-specific binding found in these antibodies. In order to quantify and compare the specificity phospho-tau antibodies and other post-translational modification site-specific antibodies in general, a measure of specificity is urgently needed. Here we report a robust flow cytometry assay using human embryonic kidney (HEK) cells that enables the determination of a specificity parameter termed {Phi}, which measures the fraction of non-specific signal in antibody binding. We validate our assay using anti-tau antibodies with known specificity profiles, and apply it to measure the specificity of 7 widely used phospho-tau antibodies (AT270, AT8, AT100, AT180, PHF-6, TG-3, and PHF-1) among others. We successfully determined the {Phi} values for all antibodies except AT100, which did not show detectable binding in our assay. Our results show that antibodies AT8, AT180, PHF-6, TG-3, and PHF-1 have {Phi} values near 1, which indicates no detectable non-specific binding. AT270 showed {Phi} value around 0.8, meaning that approximately 20% of the binding signal originates from non-specific binding. Further analyses using immunocytochemistry and western blotting confirmed the presence of non-specific binding of AT270 to non-tau proteins found in HEK cells and the mouse hippocampus. We anticipate that the quantitative approach and parameter introduced here will be widely adopted as a standard for reporting the specificity for phospho-tau antibodies, and potentially for post-translational modification targeting antibodies in general.

biochemistry↗

bioRxiv2019

Application of Volumetric Absorptive Micro Sampling to Measure Multidimensional Anti-Influenza Hemagglutinin IgG Antibodies by mPlex-Flu Assay

Recently, volumetric absorptive microsampling (VAMS) has been used for peripheral blood sampling and analyses in several fields. VAMS ensures accurate sampling by collecting a fixed blood volume (10 or 20 {micro}L) on a volumetric swab in blood spot format, and allows for long-term sample storage. The mPlex-Flu assay is a novel, multidimensional assay that measures the concentration of antibodies against multiple influenza virus hemagglutinins simultaneously strains with a small volume of serum (less than 5 {micro}L). Here we describe combining these two methods to measure multidimensional influenza antibody activity using a finger-stick and VAMS. In this study, we compared influenza antibody profiles measured from capillary blood obtained with a finger-stick, and venous whole blood collected by traditional phlebotomy from 20 subjects using the mPlex-Flu assay. We found that results with the two sampling methods were virtually identical across all influenza strains within the same subject (mean of R2 =0.9470), and that antibodies remained stable over three weeks when VAMS samples were stored at room temperature and transported using a variety of shipping methods. Additionally, VAMS sampling is an easy and highly reproducible process; when volunteers performed finger stick VAMS at home by themselves, the results of anti-HA antibody concentrations showed that they are highly consistent with sampling performed by study personnel on-site (R2 =0.9496). This novel approach provides advantages for clinical influenza vaccine studies, including ease of sampling, low cost, and high accuracy. We conclude that these methods could provide an accurate and low-cost means for monitoring the influenza virus antibody responses in large population studies.

immunology↗

bioRxiv2019

Membrane association of VAMP2 SNARE motif in cells and its regulation by different lipid phases of synaptic vesicle membrane

Vesicle associated membrane protein 2 (VAMP2) contains a conserved SNARE motif that forms helix bundles with the homologous motifs of syntaxin-1 and SNAP25 to assemble into a SNARE complex for the exocytosis of synaptic vesicles (SV). Prior to SNARE assembly, the structure of VAMP2 is unclear. Here, using in-cell NMR spectroscopy, we described the dynamic membrane association of VAMP2 SNARE motif in mammalian cells at atomic resolution, and further tracked the intracellular structural changes of VAMP2 upon the lipid environmental changes. The underlying mechanistic basis was then investigated by solution NMR combined with mass-spectrometry-based lipidomic profiling. We analyzed the lipid compositions of lipid-raft and non-raft phases of SV membrane and revealed that VAMP2 configures distinctive conformations in different phases of SV membrane. The phase of cholesterol-rich lipid rafts could largely weaken the association of SNARE motif with SV membrane and thus, facilitate vesicle docking; While in the non-raft phase, the SNARE motif tends to hibernate on SV membrane with minor activity. Our work provides a spatial regulation of different lipid membrane phases to the structure of core SNARE proteins, which deepens our knowledge on the modulation of SNARE machinery.

biophysics↗

bioRxiv2019

Clinical pattern of antibiotic overuse and misuse in primary healthcare hospitals in the southwest of China

PurposeOveruse and misuse of antibiotics are the primary risk factors for antibiotics resistance. Inadequate professional competence of primary care physicians might exacerbate these problems in China. This retrospective study aims to document the clinical pattern of antibiotics use and its overuse and misuse rates in rural primary care institutions, and to evaluate the association between antibiotics use and characteristics of the physicians and their patients.\n\nMethodsMedical records from 16 primary care hospitals in rural areas of Guizhou province, China were obtained from the Health Information System in 2018. Classification of incorrect and/or unnecessary use, escalated use and combined antibiotics use was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and the standard of USA Centers for Disease Control and Prevention. Generalized Estimating Equations were employed to determine predictive factors for inappropriate antibiotics use.\n\nResultsA total of 74,648 antibiotics prescriptions were retrieved. Uncomplicated respiratory infection was the most common disease accounting for 58.6% of all prescriptions. The main antibiotic group used was penicillins (51.5%) followed by cephalosporins and macrolides (14% each). Of 57,009 patient visits, only 8.7% of the antibiotic prescriptions were appropriate. Combined, escalated, and incorrect and/or unnecessary antibiotics use was found in 7.8%, 6.2% and 77.3% of patient visits, respectively, of which 28.7% were given intravenously. Antibiotics misuse was significantly more likely among newly employed physicians with lower levels of professional education. Adult patients and those who had public insurance had a higher risk of being prescribed incorrect and/or unnecessary antibiotics.\n\nConclusionOveruse of antibiotics for uncomplicated respiratory infection and use of cephalosporins, macrolides and injection antibiotics in primary care are the major problems of clinical practice in rural areas of Guizhou.

epidemiology↗

bioRxiv2019

Exploring the extracellular regulation of the tumor angiogenic interaction network using a systems biology model

Tumor angiogenesis is regulated by pro- and anti-angiogenic factors. Anti-angiogenic agents target the interconnected network of angiogenic factors to inhibit neovascularization, which subsequently impedes tumor growth. Due to the complexity of this network, optimizing anti-angiogenic cancer treatments requires detailed knowledge at a systems level. In this study, we constructed a tumor tissue-based model to better understand how the angiogenic network is regulated by opposing mediators at the extracellular level. We consider the network comprised of two pro-angiogenic factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), and two anti-angiogenic factors: thrombospondin-1 (TSP1) and platelet factor 4 (PF4). The models prediction of angiogenic factors distribution in tumor tissue reveals the localization of different factors and indicates the angiogenic state of the tumor. We explored how the distributions are affected by the secretion of the pro- and anti-angiogenic factors, illustrating how the angiogenic network is regulated in the extracellular space. Interestingly, we identified a counterintuitive result that the secretion of the anti-angiogenic factor PF4 can enhance pro-angiogenic signaling by elevating the levels of the interstitial and sur-face-level pro-angiogenic species. This counterintuitive situation is pertinent to the clinical setting, such as the release of anti-angiogenic factors in platelet activation or the administration of exogenous PF4 for anti-angiogenic therapy. Our study provides mechanistic insights into this counterintuitive result and highlights the role of heparan sulfate proteoglycans in regulating the interactions between angiogenic factors. This work complements previous studies aimed at understanding formation of angiogenic complexes in tumor tissue and helps in the development of anti-cancer strategies targeting angiogenesis.

systems biology↗

bioRxiv2019

Noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach using cell-free fetal DNA in maternal plasma

ObjectivesThis study was used to demonstrate the feasibility of haplotype-based noninvasive prenatal diagnosis for Hemophilia A. MethodsTwo families affected by Hemophilia A participated in our study. Maternal haplotypes associated with pathogenic mutation was built using targeted region genotypes of mother and the proband. Combined with maternal pathogenic haplotype, a Hidden Markov Model was constructed to deduce fetal haplotype using high-coverage targeted sequencing of maternal plasma. The presence of pathogenic haplotype in male indicated affected fetus, in female indicated carrier. Prenatal diagnosis was confirmed with amniocentesis by long distance PCR. ResultsThe haplotype-based noninvasive prenatal diagnosis was successfully performed in Hemophilia A. One fetus was identified to be normal, another fetus was identified as carrier, and the results were confirmed by amniocentesis . ConclusionOur research demonstrated the feasibility of noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach.

molecular biology↗

bioRxiv2019

Pair-wise Comparison Analysis for Multiple Pool-sep: an efficient method identified anthocyanin biosynthesis genes in rice pericarp

The complex traits are derived from multiple genes and exhibit a large variety of phenotypes. High-throughput sequencing technologies have become the new strategies for mapping the important traits of crops. However, these methods have their own disadvantages and limitations. Here we introduced Pair-wise Comparison Analysis for Multiple Pool-seq (PCAMP) for mapping the candidate genomic regions involved in anthocyanin biosynthesis in rice pericarp. In this protocol, the second filial generation (F2) populations obtained by crossing two parents with different target traits were divided into n (n>=3) subpopulations according to their phenotypes. Thirty phenotypically identical individuals were selected from each subpopulation and DNA samples were extracted to form a pool for sequencing. Finally, we compared the SNP-index between every two Pool-seqs to map the candidate genomic regions. We applied PCAMP to analyse F2 populations and successfully identified five known genes and five new candidate genomic regions for anthocyanin biosynthesis in rice pericarp. These results demonstrate that PCAMP is an efficient new method for dissecting the complex traits of crops.

molecular biology↗

bioRxiv2019

Programming conventional electron microscopes for solving ultrahigh-resolution structures of small and macro-molecules

Microcrystal electron diffraction (MicroED) is becoming a powerful tool in determining the crystal structures of biological macromolecules and small organic compounds. However, wide applications of this technique are still limited by the special requirement for radiation-tolerated movie-mode camera and the lacking of automated data collection method. Herein, we develop a stage-camera synchronization scheme to minimize the hardware requirements and enable the use of the conventional electron cryo-microscope with single-frame CCD camera, which ensures not only the acquisition of ultrahigh-resolution diffraction data but also low cost in practice. This method renders the structure determination of both peptide and small organic compounds at ultrahigh resolution up to ~0.60 [A] with unambiguous assignment of nearly all hydrogen atoms. The present work provides a widely applicable solution for routine structure determination of MicroED, and demonstrates the capability of the low-end 120kV microscope with a CCD camera in solving ultra-high resolution structures of both organic compound and biological macromolecules.

biophysics↗

bioRxiv2019

OsLUGL involved in floral development through regulating auxin level and OsARFs expression in rice (Oryza sative L.)

Specification of floral organ identity is critical for floral morphology and inflorescence architecture. Floral organ identity in plants is controlled by floral homeotic A/B/C/D/E-class genes. Although multiple genes regulate floral organogenesis our understanding of the regulatory network remains fragmentary. Here, we characterized rice floral organ gene KAIKOUXIAO (KKX), mutation of which produces an uncharacteristic open hull, abnormal seed, and semi-sterility. KKX encodes a putative LEUNIG-like (LUGL) transcriptional co-repressor. OsLUGL is preferentially expressed in young panicles and its protein can interact with OsSEU, which functions were reported as an adaptor for LEUNIG. OsLUGL-OsSEU functions together as a transcriptional regulatory complex to control organ identity specification through regulation of MADS-box genes. During this process, SEP3 (such as OsMADS8) and AP1 (such as OsMADS18) serve as the DNA-binding partner of OsLUGL-OsSEU complex. Further studies indicated that OsMADS8 and OsMADS18 could bind the promoter of OsGH3-8 and regulate its expression. The altered expression of OsGH3-8 caused the increased auxin level and the decreased expression of OsARFs. Overall, our results demonstrate a possible pathway whereby OsLUGL-OsSEU-OsAP1-OsSEP3 complex as a transcriptional regulator by targeting the promoter of OsGH3-8 directly, affecting auxin level, OsARFs expression level and thereby influencing floral development. These findings provide a valuable insight into the molecular functions of OsLUGL in rice floral development. HighlightOsLUGL through forming OsLUGL-OsSEU-OsAP1-OsSEP3 complex regulate OsGH3-8 expression, and regulate auxin level and OsARFs expression indirectly. This work is a new insight to floral development molecular mechanism.

genetics↗