Biology subjects

Sin, Y.-C.

Publications and source records attributed to Sin, Y.-C..

3 recordsLinked to original sources

bioRxiv2024

Sorbate Induces Lysine Sorbylation Through Non-Canonical Activities of Class I HDACs to Regulate the Expression of Inflammation Genes

Metabolic and environmental factors may impact gene expression through the production of active metabolites and epigenetic modifications of histones and transcription factors. In this study, we discovered that cellular uptake of sorbate, an FDA-approved and widely used food preservative, can induce lysine sorbylation (Ksor), a new posttranslational modification and epigenetic mark. We identified over 40 Ksor sites on core histones from mammalian cells and tissue upon sorbate uptake and further showed that the dynamics of histone Ksor could be regulated by the non-canonical activities of Class I histone deacetylases (HDAC1-3). We demonstrated that Class I HDACs catalyzed sorbylation upon sorbate uptake and desorbylation in the absence of sorbate both in vitro and in vivo. Sorbate uptake in mice livers led to a significant increase in histone Ksor without affecting overall histone acetylation, which correlated with the decreased expression of genes in inflammation signaling pathways. Accordingly, sorbate treatment in macrophage RAW264.7 cells upon LPS stimulation dose-dependently downregulated the expression of proinflammatory genes and production of nitric oxide. Global proteomic profiling revealed widespread lysine sorbylation substrates in diverse metabolic and signaling pathways and identified RelA (p65), a component of the NF-B complex, and its interacting proteins as bona fide Ksor targets. Sorbate treatment significantly decreased NF-B transcriptional activities in response to LPS stimulation in RAW264.7 cells. Taken together, our study demonstrated a non-canonical mechanism of sorbate uptake in regulating epigenetic histone modifications and inflammatory gene expression.

biochemistry↗

bioRxiv2023

Neutrophil extracellular traps formation is associated with postoperative complications in neonates and infants undergoing congenital cardiac surgery

Pediatric patients with congenital heart diseases (CHD) often undergo surgical repair on cardiopulmonary bypass (CPB). Despite a significant medical and surgical improvement, the mortality of neonates and infants remains high. Damage-associated molecular patterns (DAMPs) are endogenous molecules released from injured/damaged tissues as danger signals. We examined 101 pediatric patients who underwent congenital cardiac surgery on CPB. The mortality rate was 4.0%, and the complication rate was 31.6%. We found that neonates/infants experienced multiple complications most, consistent with the previous knowledge. Neonates and infants in the complication group had received more transfusion intraoperatively than the non-complication arm with lower maximum amplitude (MA) on rewarming CPB thromboelastography (TEG). Despite TEG profiles were comparable at ICU admission between the two groups, the complication arm had higher postoperative chest tube output, requiring more blood transfusion. The complication group showed greater neutrophil extracellular traps (NETs) formation at the end of CPB and postoperatively. Plasma histones and high mobility group box 1 (HMGB1) levels were significantly higher in the complication arm. Both induced NETs in vitro and in vivo. As histones and HMGB1 target Toll-like receptor (TLR)2 and TLR4, their mRNA expression in neutrophils was upregulated in the complication arm. Taken together, NETs play a major role in postoperative complication in pediatric cardiac surgery and would be considered a target for intervention. Key pointsO_LINeonates and infants showed highest postoperative complications with more upregulation of inflammatory transcriptomes of neutrophils. C_LIO_LINeonates and infants with organ dysfunction had more NETs formation with higher plasma histones and HMGB1 levels. C_LI

immunology↗

bioRxiv2020

Protein hyperacylation links mitochondrial dysfunction with nuclear organization

Cellular metabolism is linked to epigenetics, but the biophysical effects of metabolism on chromatin structure and implications for gene regulation remain largely unknown. Here, using a broken tricarboxylic acid (TCA) cycle and disrupted electron transport chain (ETC) exemplified by succinate dehydrogenase subunit C (SDHC) deficiency, we investigated the effects of metabolism on chromatin architecture over multiple distance scales [nucleosomes ([~]102 bp), topologically-associated domains (TADs; [~]105 - 106 bp), and chromatin compartments (106 - 108 bp)]. Metabolically-driven hyperacylation of histones led to weakened nucleosome positioning in multiple types of chromatin, and we further demonstrate that lysine acylation directly destabilizes histone octamer-DNA interactions. Hyperacylation of cohesin subunits correlated with decreased mobility on interphase chromatin and increased TAD boundary strength, suggesting that cohesin is metabolically regulated. Erosion of chromatin compartment distinctions reveals metabolic regulation of chromatin liquid-liquid phase separation. The TCA cycle and ETC thus modulate chromatin structure over multiple distance scales.

cell biology↗