Biology subjects

Yoo, S.-H.

Publications and source records attributed to Yoo, S.-H..

9 recordsLinked to original sources

bioRxiv2026

FBXL21 regulates diurnal proteostasis and stress response by targeting DNAJB6 and client proteins

Circadian regulation of proteostasis, a key determinant of muscle health, remains poorly understood. Here, we identified DNAJB6, an Hsp40 (DnaJ) co-chaperone, as a substrate of the circadian E3 ligase FBXL21. FBXL21 mediated the ubiquitination-dependent proteasomal degradation of both DNAJB6 and its client proteins including Desmin; causative mutations of DNAJB6 in myopathies, however, rendered resistance to FBXL21-directed degradation. Fbxl21 KO C2C12 cells displayed aberrant accumulation of Desmin, and showed aggravated cytoplasmic accumulation of TDP-43, another DNAJB6 client protein, in heat shock response. Under timed exercise as a physiological stressor, WT mice displayed robust diurnal rhythms in the levels of stress granule markers (G3BP1 and FUS) and TDP-43 as a function of exercise timing. In contrast, the Fbxl21 hypomorph Psttm mutant mice showed elevated expression of these proteins without exercise, which was exacerbated under exercise-induced stress conditions; importantly, these abnormalities were rescued by skeletal muscle-specific FBXL21 expression. Our study elucidates a novel diurnal regulatory mechanism of skeletal muscle proteostasis via FBXL21 as a chaperone-linked E3 ligase, highlighting the FBXL21-DNAJB6 axis as a potential therapeutic target for myopathies.

cell biology↗

bioRxiv2026

DHHC3-dependent S-Acylation of CRY1 regulates its subcellular localization and repressor function in the circadian clock

The circadian clock is essential for maintaining cellular homeostasis and physiological fitness. At the molecular level, core clock proteins function via transcriptional-translational feedback loops in the cellular oscillator, and are highly regulated by post-translational modifications. Our unbiased screening of core clock proteins revealed that Cryptochrome 1 (CRY1), the central transcriptional repressor in the circadian clock, undergoes a novel post-translational modification known as S-acylation. We show that this reversible lipidation of CRY1 is required for its nuclear import and interaction with key clock components. Further, we mapped four cysteine residues as CRY1 S-acylation sites and identified DHHC3 as the primary protein acyltransferase for CRY1. Importantly, loss of CRY1 S-acylation, either via cysteine mutagenesis or genetic deletion of DHHC3, impaired CRY1 repressor function and consequently cellular circadian rhythms, suggesting that dynamic S-acylation couples cytoplasmic regulation of CRY1 and its transcriptional repressor function in the nucleus. Together, our findings identify S-acylation as a previously unknown post-translational modification of CRY1 critical for circadian clock function and establish DHHC3 as a pivotal circadian regulatory enzyme. Targeting CRY1 S-acylation or its regulatory enzymes may constitute an innovative therapeutic approach against clock-associated diseases.

biochemistry↗

bioRxiv2026

Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by alveolar destruction, impaired epithelial regeneration and chronic inflammation. While circadian disruption has been linked to COPD pathogenesis, the cellular mechanisms remain unclear. Here, we identify the core clock components Cryptochrome 1 and 2 (Cry1/2) as essential regulators of alveolar epithelial cell proliferation and pulmonary immune homeostasis. Cry1/2 double knockout (dKO) mice exhibit spontaneous emphysema-like pathology, including airspace enlargement, increased lung compliance, and inflammatory cell infiltration without environmental insults. Mechanistically, Cry1/2-deficient alveolar epithelial cells display reduced proliferative capacity, and transcriptomic profiling revealed a pronounced shift toward a more proximal airway-like phenotype. Notably, these cells share a gene signature with human COPD lungs in pathways involving immune regulation. Furthermore, Cry1/2-deficient macrophages show elevated responsiveness to LPS. Bone marrow (BM) transplantation revealed that mice receiving Cry1/2 dKO BM suffer from enhanced lung inflammation without airspace enlargement, supporting a critical role of epithelial Cry1/2 in maintaining alveolar integrity. Importantly, treatment with Nobiletin, a circadian rhythm-modulating compound, mitigates NF-{kappa}B activation and ameliorates lung inflammation and structural damage in Cry1/2 dKO mice. These findings establish CRY1/2 as critical circadian regulators of epithelial cell proliferation and immune homeostasis, and highlight the therapeutic potential of targeting circadian pathways in COPD.

genetics↗

bioRxiv2025

The nutritional value of invertebrate aquatic foods

Aquatic invertebrates are a diverse, nutrient-dense, and socio-ecologically important food whose contribution to human nutrition is frequently overlooked. We quantify their contribution to global nutrient supplies and estimate the nutrient content of >50,000 macroinvertebrate species. Current aquatic invertebrate production supplies the equivalent annual requirement for >6 billion people in terms of vitamin B12 and selenium; >1 billion people for copper, omega 3 fatty acids, iodine and zinc; and >100 million people for nutrients such as vitamins B2 and B3, iron, manganese, and magnesium. Nutrient composition differs among taxonomic groups, consumption patterns, and environmental and life-history factors. Our study highlights the benefits of integrating aquatic invertebrates into dietary portfolios across global societies, mainstreaming their nutritional importance in development projects, sustainability assessments and food policy.

ecology↗

bioRxiv2024

TGF-β expressed by M2 macrophages promotes wound healing by inhibiting TSG-6 expression by mesenchymal stem cells

Wound healing involves the collaboration of multiple cells, including macrophages and fibroblasts, and requires the coordination of cytokines, growth factors, and matrix proteins to regulate the repair response. In this study, we investigated how M2 macrophages regulate expression of the anti-fibrotic and anti-inflammatory regulator tumor necrosis factor- (TNF-)-stimulated gene 6 (TSG-6) secreted by adipose tissue-derived stem cells (ASCs) during wound healing. Interleukin (IL)-4/IL-13, which is used to differentiate macrophage M2 phenotypes, increases TSG-6 in ASCs; however, M2 macrophages significantly decrease TSG-6 in ASCs. Transforming growth factor (TGF)-{beta} expression was increased, and TNF- expression was decreased in M2 macrophages. TGF-{beta} inhibited IL-4/IL-13-induced ASC TSG-6 expression. In addition, TSG-6 suppressed TGF-{beta}-triggered wound closure and fibrogenic responses in LX-2 cells. Collectively, TSG-6 inhibited wound healing, but M2 macrophage-expressed TGF-{beta} prevented TSG-6 production from ASCs, which ultimately helped wound healing. Our results indicate that the balance of TNF- and TGF-{beta} levels during wound healing regulates TSG-6 production from ASCs, which may ultimately modulate the healing process. Our study findings could contribute to novel therapeutic strategies that manipulate the delicate balance between TNF- and TGF-{beta} to enhance wound repair and mitigate fibrosis.

cell biology↗

bioRxiv2024

Population connective field modeling reveals retinotopic visual cortex organization in the prenatal human brain

The visual space is sampled by cortical field maps in which nearby neuronal populations encode nearby locations of images received from the retina. Whether retinotopic cortical organization already emerges in the neonatal or even prenatal human brain is currently unknown. To answer this question in vivo, we applied population connective field modeling to 871 resting-state functional magnetic resonance imaging datasets ranging from prenatal to young adult age. We found topographically organized eccentricity and polar angle connectivity maps in V2 and V3 of the visual cortex as early as the 21st week of gestation. These results highlight that human proto-retinotopic cortical maps develop in the second trimester of pregnancy, predating visual experience.

neuroscience↗

bioRxiv2020

A novel bioinformatics approach to reveal the role of circadian oscillations in AD development

Altered circadian gene expression may contribute to Alzheimers disease (AD) progression. Unfortunately, sampling the central nervous system (CNS) at multiple time points is not feasible. Moreover, there are no AD-related time-series transcriptome datasets available for studying these circadian patterns and their impacts on AD development. In this study, we introduce a novel computational platform, Event-driven Sample Ordering for Circadian Variation Detection (ESOCVD), to reveal rhythmic patterns of gene expression of AD using untimed transcriptome datasets. ESOCVD was applied to 20 untimed gene expression profiles of 16 brain regions from approximately 3000 AD patients in public transcriptome databases. Our analysis revealed five types of circadian alteration patterns in ~2,000 circadian genes in different brain regions of AD patients. Further analyses of additional databases confirmed that our analytical platform can be applied to identify the evolutionary dynamics of circadian variation during the process of AD development. Through the gene expression correlation analysis for our 8 circadian genes identified from AMP-AD MSBB cohorts, we identified stage-specifically enriched biological processes with anticipated context. Gene expression analysis of AD mouse brain tissues further substantiated the predictions of the ESOCVD model. In summary, ESOCVD is highly versatile in bridging circadian research and precision medicine.

bioinformatics↗

bioRxiv2018

Tissue-specific BMAL1 cistromes reveal that enhancer-enhancer interactions regulate rhythmic transcription

AbtsractThe mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, due to differences in chromatin accessibility between tissues and co-binding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription not only relies on the activity of BMAL1 cis-regulatory elements (CREs), but also on the activity of neighboring CREs. Characterization of the physical interactions between BMAL1 CREs and other CREs in the mouse liver reveals that interactions are quite stable, and that BMAL1 controls rhythmic transcription by regulating the activity of other CREs. This supports that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.

genetics↗

bioRxiv2017

Daam2 Driven Degradation Of VHL Promotes Gliomagenesis

Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. These in silico insights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.\n\nStatement of SignificanceWe found that the glial developmental factor Daam2 promotes glioma tumorigenesis by suppressing VHL expression. Our studies show, for the first time, a regulatory mechanism that operates upstream of VHL in cancer and provides an explanation for how VHL expression is extinguished in tumors that do not have inactivating mutations.

cancer biology↗