Biology subjects

Jeon, J.

Publications and source records attributed to Jeon, J..

33 records · Page 2Linked to original sources

bioRxiv2023

Single-molecule analysis of transcription activation: Dynamics of SAGA co-activator recruitment

Transcription activators are said to stimulate gene expression by "recruiting" coactivators to promoters, yet this term fits several different kinetic models. To directly analyze dynamics of activator-coactivator interactions, single-molecule microscopy was used to image promoter DNA, a transcription activator, and the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex within nuclear extract. SAGA readily, but transiently, binds nucleosome-free DNA without activator, while chromatin template association occurs nearly exclusively when activator is present. On both templates, activator increases SAGA association rates by up to an order of magnitude, and dramatically extends its dwell times. These effects reflect direct interactions with the transactivation domain, as VP16 or Rap1 activation domains produce different SAGA dynamics. Despite multiple bromodomains, acetyl-CoA or histone H3/H4 tail acetylation only modestly improves SAGA binding. Unexpectedly, histone acetylation more strongly affects activator residence. Our studies thus reveal two modes of SAGA interaction with the genome: a short-lived activator-independent interaction with nucleosome-free DNA, and a state tethered to promoter-bound transcription activators that can last up to several minutes.

molecular biology↗

bioRxiv2023

KoNA: Korean Nucleotide Archive as a New Data Repository for Nucleotide Sequence Data

During the last decade, generation and accumulation of petabase-scale high-throughput sequencing data have resulted in ethical and technical challenges, including access to human data, and transfer, storage, and sharing of enormous amount of data. To promote data-driven research in biology, the Korean government announced that all the biological data generated from government-funded research projects should be deposited in the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. We introduce the Korean Nucleotide Archive (KoNA), a repository for nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next generation sequencing data from several national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure (SOP) was adopted, which is similar to the International Nucleotide Sequence Database Collaboration. The SOP includes quality control processes for submitted data and metadata using an automated pipeline followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed in a cloud-computing service for genomic data analysis called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances data experience including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea, but also provides datasets to researchers globally and contribute to advances in genomics. KoNA is available at https://www.kobic.re.kr/kona/.

genomics↗

bioRxiv2023

Genetic and transcriptomic analysis of hyphal constriction based on a novel assay method in the rice blast fungus

An ability of fungi to undergo hyphal constriction is important for fungal ecology and diseases. In the rice blast fungus, Magnaporthe oryzae, hyphal constriction is required to traverse host cell junctions through pit fields. However, little is known about genetic underpinnings of hyphal constriction, except the requirement of a mitogen-activated protein kinase, Pmk1. Here we demonstrate that a simple in vitro assay based on nitrocellulose membrane allows investigation of the genetic basis for hyphal constriction. Using the assay, we found that the constriction limit of M. oryzae hypha lies between 0.22 and 0.3 m, and that a histone modification might be involved in hyphal constriction. RNA-seq experiments combining our assay and {Delta}pmk1 showed that hyphal constriction relies on transcriptional changes of genes implicated primarily in membrane and cell wall-related cellular processes in Pmk1-dependent and/or Pmk1-independent manner. Furthermore, our assays with diverse fungal species suggest correlation between hyphal constriction and fungal lifestyles. Our study reveals that hyphal constriction can be induced without host-derived cues and provides molecular and evolutionary insights into a fundamental process to infection of host plant.

microbiology↗

bioRxiv2022

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

We present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest whole genomic resource of Koreans. Korea4K provides 45,537,252 variants and encompasses most of the common and rare variants in Koreans. We identified 1,356 new geno-phenotype associations which were not found by the previous Korea1K dataset. Phenomics analyses revealed 24 genetic correlations, 1,131 pleiotropic variants, and 127 causal relationships from Mendelian randomization. Moreover, the Korea4K imputation reference panel showed a superior imputation performance to Korea1K. Collectively, Korea4K provides the most extensive genomic and phenomic data resources for discovering clinically relevant novel genome-phenome associations in Koreans.

genomics↗

bioRxiv2022

Phosphatidylserine controls synaptic targeting and membrane stability of ASIC1a

Phospholipid-protein interaction is highly specialized at the membranous nanodomains and critical for membrane receptor signaling. Calcium-permeable acid-sensing ion channel isoform 1a (ASIC1a) is a major neuronal proton sensor that contributes to synaptic plasticity. The functional outcome of ASIC1a is dependent on its surface targeting in synaptic subdomains; however, the lipid environment for ASIC1a and its role in channel targeting remain poorly understood. Here, we report that anionic phosphatidylserine (PS) is enriched in dendritic spines during neurodevelopment and it directly binds to ASIC1a through an electrostatic interaction with a di-arginine motif at ASIC1a C-terminus. PS regulates the membrane targeting and function of ASIC1a, which are both strongly suppressed by inhibition of PS synthesis. In cortical neuron dendrites, both PS and ASIC1a are predominately localized to peri-synaptic sites of spine heads, surrounding instead of overlapping with postsynaptic markers, PSD-95 and GluN1. Uncoupling the interaction between PS and ASIC1a by changing the charges to neutral or acidic at the di-arginine PS-binding motif, or applying a membrane penetrating competing peptide, caused mistargeting of ASIC1a at the synaptic sites, an overall increase in internalization and/or cytoplasmic accumulation of ASIC1a, and a decrease in its channel function. Together, our results provide novel insights on lipid microenvironment that governs ASIC1a expression and function at the membrane surface, especially peri-synaptic regions of dendritic spines, through an electrostatic interaction with anionic phospholipids.

neuroscience↗

bioRxiv2021

Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress response, and aging

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode, Caenorhabditis elegans, have shown that the Axin homolog, PRY-1, plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Eight of the genes (ard-1, rpn-7, cpz-1, his-7, cdk-1, rnr-1, clsp-1, and spp-1), when knocked down by RNA interference, efficiently suppressed the plate-level multivulva phenotype of pry-1 mutants. In every case, other than clsp-1 and spp-1, the ectopic vulval precursor cell (VPC) induction was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that except for clsp-1, the genes participate in one or more pry-1-mediated biological events. While four of them (cpz-1, his-7, cdk-1, and rnr-1) function in VPC induction, stress response, and aging, the other three (spp-1, ard-1, and rpn-7) are specific to one or more of these processes. Further analysis of the genes involved in aging showed that his-7, cdk-1, and rnr-1 also interacted with daf-16/FOXO. The results of genetic epistasis experiments suggested that his-7 functions upstream of daf-16, whereas cdk-1 and rnr-1 act downstream of the pry-1-daf-16 pathway. Altogether, these findings demonstrate the important role of pry-1 suppressors in C. elegans. Given that all of the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin under normal and disease states.

genetics↗

bioRxiv2020

Curvature of the retroviral capsid assembly is modulated by a molecular switch

During the maturation step, the capsid proteins (CAs) of a retrovirus assemble into polymorphic capsids, whose acute curvature is largely determined by insertion of 12 pentamers into the hexameric lattice. Despite years of intensive research, it remains elusive how the CA switches its conformation between the quasi-equivalent pentameric and hexameric assemblies to generate the acute curvature in the capsid. Here we report the high-resolution structural model of the RSV CA T=1 capsid. By comparing with our prior model of the RSV CA tubular assembly consisting entirely of hexameric lattices, we identify that a dozen of residues are the key to dictate the incorporation of acute curvatures in the capsid assembly. They undergo large torsion angle changes, which result a 34{degrees} rotation of the C-terminal domain relative to its N-terminal domain around the flexible interdomain linker, without substantial changes of either the conformation of individual domains or the assembly contact interfaces. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/424437v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@40cf38org.highwire.dtl.DTLVardef@e490beorg.highwire.dtl.DTLVardef@1dae0c5org.highwire.dtl.DTLVardef@dac850_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2020

Biomarker potential of real-world voice signals to predict abnormal blood glucose levels

BackgroundVoice signal analysis is an emerging non-invasive technique to examine health conditions, and is implemented in various real-life applications and devices. The purpose of this study was to evaluate the association of voice signals with blood glucose levels in healthy individuals. The study aimed to investigate the longitudinal stabilities of voice signals and identify voice biomarkers to predict abnormal blood glucose levels. MethodsWe created voice profiles composed of 17,552,688 voice signals from 44 participants and their 1,454 voice recordings. From each voice recording, 12,082 voice-features were extracted. Longitudinal stabilities of voice-features were quantified using linear mixed-effect modelling. Voice-features that showed significant difference between different blood glucose levels, strong intra-stability and the ability to make distinct choice in decision trees were selected as voice biomarker. Voice biomarkers were fed into a multi-class random forest classifier to predict high, normal, and low blood glucose levels. FindingsIn total, 196 voice biomarkers were characterized. Results showed a predictive model with an overall accuracy of 78.66%, overall AUC of 0.83 (95% confidence interval is 0.80 - 0.85), and 0.41 of Matthews Correlation Coefficient (MCC) to discriminate three different blood glucose levels in an independent test set. InterpretationOur voice biomarkers could serve as a noninvasive and conventional surrogate of blood glucose monitoring in daily life as well as a screening tool to estimate potential risk of poor glycemic control. FundingThis research was internally funded and received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

systems biology↗

bioRxiv2020

Label-free three-dimensional observations and quantitative characterisation of on-chip vasculogenesis using optical diffraction tomography

Label-free, three-dimensional (3D) quantitative observations of on-chip vasculogenesis were achieved using optical diffraction tomography. Exploiting 3D refractive index maps as an intrinsic imaging contrast, the vascular structures, multicellular activities, and subcellular organelles of endothelial cells were imaged and analysed throughout vasculogenesis to characterise mature vascular networks without exogenous labelling. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/892620v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@12a786eorg.highwire.dtl.DTLVardef@14892dforg.highwire.dtl.DTLVardef@1a28091org.highwire.dtl.DTLVardef@1a6e9df_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

IQSEC3 Mediates Npas4-dependent GABAergic Synaptic Transmission and Depressive-like Behavior

Organization of mammalian inhibitory synapses is thought to be crucial for normal brain functions, but the underlying molecular mechanisms have been still incompletely understood. IQSEC3 (IQ motif and Sec7 domain 3) is a guanine nucleotide exchange factor for ADP-ribosylation factor (ARF-GEF) that directly interacts with gephyrin. Here, we show that GABAergic synapse-specific transcription factor, Npas4 (neuronal PAS domain protein 4) directly binds to the promoter of Iqsec3 and regulates its transcription. Strikingly, an enriched environment (EE) induced Npas4 upregulation and concurrently increased IQSEC3 protein levels specifically in mouse CA1 stratum oriens layer somatostatin (SST)-expressing GABAergic interneurons, which are compromised in Npas4-knockout (KO) mice. Moreover, expression of wild-type (WT) IQSEC3, but not a dominant-negative (DN) ARF-GEF-inactive mutant, rescued the decreased GABAergic synaptic transmission in Npas4-deficient SST interneurons. Concurrently, expression of IQSEC3 WT normalized the altered GABAergic synaptic transmission in dendrites, but not soma, of Npas4-deficient CA1 pyramidal neurons. Furthermore, expression of IQSEC3 WT, but not IQSEC3 DN, in SST-expressing interneurons in CA1 SST Npas4-KO mice rescued the altered anxiety-like behavior. Collectively, our results suggest that IQSEC3 is a key GABAergic synapse component that is directed by Npas4 activity- and ARF activity-dependent gene programs in SST-expressing interneurons to orchestrate the functional excitation-to-inhibition balance.

neuroscience↗

bioRxiv2018

MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma

Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX-histone chaperone complex and that induced by MYCN-mediated metabolic reprogramming leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.

cancer biology↗

bioRxiv2018

TGFam-Finder: An optimal solution for target-gene family annotation in eukaryotic genomes

Whole genome annotation errors that omit essential protein-coding genes hinder further research. We developed Target Gene Family Finder (TGFam-Finder), an optimal tool for structural annotation of protein-coding genes containing target domain(s) of interest in eukaryotic genomes. Large-scale re-annotation of 100 publicly available eukaryotic genomes led to the discovery of essential genes that were missed in previous annotations. An average of 117 (346%) and 148 (45%) additional FAR1 and NLR genes were newly identified in 50 plant genomes. Furthermore, 117 (47%) additional C2H2 zinc finger genes were detected in 50 animal genomes including human and mouse. Accuracy of the newly annotated genes was validated by RT-PCR and cDNA sequencing in human, mouse and rice. In the human genome, 26 newly annotated genes were identical with known functional genes. TGFam-Finder along with the new gene models provide an optimized platform for unbiased functional and comparative genomics and comprehensive evolutionary study in eukaryotes.

bioinformatics↗

bioRxiv2018

Comparative Transcriptomic and Metabolomic Analyses in Response to Cold in Tartary Buckwheat (Fagopyrum tataricum)

Plants recognize multiple environmental signals that lead to substantial changes in the regulation of primary and secondary metabolism in order to adapt to environmental stresses. In this study, we investigate the effects of cold on the metabolome and transcriptome of tartary buckwheat, focusing on the phenylpropanoid biosynthetic pathway. Using RNA-sequencing analysis of the cold-regulated transcriptome of buckwheat, we identified several phenylpropanoid biosynthetic transcripts that accumulated in response to cold. To confirm the transcriptome data, we analyzed the expression of the phenylpropanoid biosynthetic transcripts in cold-treated buckwheat and showed that all the phenylpropanoid biosynthetic transcripts were upregulated in coldtreated buckwheat seedlings with the exception of FtDFR. From the metabolic profiling based on the GC-TOF-MS analysis, we show that most of the sugars and their derivatives significantly increase in response to cold, while some of amino acids and their derivatives decrease in cold-treated plants. Some organic acids derived from the tricarboxylic acid (TCA) cycle increased in the cold-treated plants compared with in the plants grown at 25{degrees}C. In particular, the contents of anthocyanins and proanthocyanidins were significantly increased by cold treatment. In summary, these results indicate that the metabolome and transcriptome of tartary buckwheat are extensively affected by cold stresses.\n\nHighlightUsing the RNA-sequencing data and the metabolic profiling analysis, we identified the changes that occur in the transcriptome and metabolome of tartary buckwheat in response to cold, focusing on the flavonoid biosynthetic pathway.\n\nAbbreviations

systems biology↗

bioRxiv2017

Computational docking reveals evolutionary conservation of a specific interaction between 15d-Prostaglandin-J2 and eIF4A.

15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2) is anti-inflammatory/antineoplastic prostaglandin which functions through covalent binding to cysteine residues of various target proteins. We previously showed that 15d-PGJ2 mediated anti-inflammatory responses are dependent on the translational inhibition through its interaction with eIF4A. Binding of 15d-PGJ2 to eIF4A specifically blocks the interaction between eIF4G and eIF4A leads to the formation of stress granules (SGs), which cluster mRNAs with inhibited translation. Here we show that the binding between 15d-PGJ2 and eIF4A specifically blocks the interaction between the MIF4G domain of eIF4G and eIF4A. To reveal the mechanism of this interaction, we used computational simulation-based docking studies and identified that the carboxyl tail of 15d-PGJ2 could stabilize the binding of 15d-PGJ2 to eIF4A through arginine 295 of eIF4A, which is the first suggestion that the 15d-PGJ2 tail play a physiological role. Interestingly, the putative 15d-PGJ2 binding site on eiF4A is conserved across many species, suggesting a biological role. Our data propose that studying 15d-PGJ2 and its targets will may uncover new therapeutic approaches in anti-inflammatory drug discovery.

molecular biology↗

bioRxiv2017

Multiple reference genome sequences of hot pepper reveal the massive evolution of plant disease resistance genes by retroduplication

Transposable elements (TEs) provide major evolutionary forces leading to new genome structure and species diversification. However, the role of TEs in the expansion of disease resistance gene families has been unexplored in plants. Here, we report high-quality de novo genomes for two peppers (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum). Dynamic genome rearrangements involving translocations among chromosome 3, 5 and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs exhibited great abundance across the angiosperms, with most cases lineage-specific and thus recent events. Our study revealed that retroduplication has played key roles in the emergence of new disease-resistance genes in plants.

plant biology↗