Biology subjects

Jung, S. A.

Publications and source records attributed to Jung, S. A..

3 recordsLinked to original sources

bioRxiv2025

MeCP2 regulates cell type-specific functions of depressive-like symptoms in the nucleus accumbens

MeCP2 (methyl CpG binding protein 2) is a transcriptional regulator that modulates gene expression in response to environmental stimuli. Although recent studies have implicated MeCP2 in stress responses and depression, its precise role is not completely understood. In this study, we identify a cell type-specific function of MeCP2 in the regulation of depression-like symptoms within the nucleus accumbens (NAc), a key brain region for emotional and stress processing. We observed differential MeCP2 expression in distinct cell populations of the NAc following chronic restraint stress (CRS) and investigated the behavioral and electrophysiological consequences of cell type-specific MeCP2 manipulation. We also explored the molecular mechanisms by which MeCP2 alleviates depression-like symptoms in the NAc and associated neural circuit regions through cell type-specific profiling of the spatial transcriptome. Our findings demonstrate that MeCP2 contributes to synaptic and circuit-level regulation in a cell type-specific manner within the NAc and ultimately mitigates CRS-induced depression-like behaviors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/666523v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1ae5875org.highwire.dtl.DTLVardef@1319231org.highwire.dtl.DTLVardef@174ef60org.highwire.dtl.DTLVardef@fb061_HPS_FORMAT_FIGEXP M_FIG Graphical abstract.Schematic Summary of the functional role of accumbal MeCP2 C_FIG

neuroscience↗

bioRxiv2019

Ethanolamine regulates CqsR quorum-sensing signaling in Vibrio cholerae

The pathogen that causes cholera, Vibrio cholerae, uses the cell-cell communication process known as quorum sensing (QS) to regulate virulence factor production and biofilm formation in response to changes in population density and complexity. QS is mediated through the detection of extracellular chemical signals called autoinducers. Four histidine kinases, LuxPQ, CqsS, CqsR and VpsS, have been identified as receptors to activate the key QS regulator LuxO at low cell density. At high cell density, detection of autoinducers by these receptors leads to deactivation of LuxO, resulting in population-wide gene expression changes. While the cognate autoinducers that regulate the activity of CqsS and LuxQ are known, the signals that regulate CqsR have not been determined. Here we show that the common metabolite ethanolamine specifically interacts with the ligand-binding CACHE domain of CqsR in vitro and induces the high cell-density QS response through CqsR kinase inhibition in V. cholerae cells. We also identified residues in the CqsR CACHE domain important for ethanolamine detection and signal transduction. Moreover, mutations disrupting endogenous ethanolamine production in V. cholerae delay the onset of, but do not abolish, the high cell-density QS gene expression. Finally, we demonstrate that modulation of CqsR QS response by ethanolamine occurs inside animal hosts. Our findings suggest that V. cholerae uses CqsR as a dual-function receptor to integrate information from the self-made signals as well as exogenous ethanolamine as an environmental cue to modulate QS response.\n\nIMPORTANCEMany bacteria use quorum sensing to regulate cellular processes that are important for their survival and adaptation to different environments. Quorum sensing usually depends on the detection on chemical signals called autoinducers made endogenously by the bacteria. We show here ethanolamine, a common metabolite made by various bacteria and eukaryotes, can modulate the activity of one of the quorum-sensing receptors in Vibrio cholerae, the etiological agent of the disease cholera. Our results raise the possibility that V. cholerae or other quorum-sensing bacteria can combine environmental sensing and quorum sensing to control group behaviors.

microbiology↗

bioRxiv2019

HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans

Heat shock factor 1 (HSF-1) is a component of the heat shock response pathway that is induced by cytoplasmic proteotoxic stress. In addition to its role in stress response, HSF-1 also acts as a key regulator of the rate of organismal aging. Overexpression of HSF-1 promotes longevity in C. elegans via mechanisms that remain less understood. Moreover, genetic ablation of a negative regulator of HSF-1, termed as heat shock factor binding protein 1 (HSB-1), results in hsf-1-dependent life span extension in animals. Here we show that in the absence of HSB-1, HSF-1 acquires increased DNA binding activity to its genomic target sequence. Using RNA-Seq to compare the gene expression profiles of the hsb-1 mutant and hsf-1 overexpression strains, we found that while more than 1,500 transcripts show [≥]1.5-fold upregulation due to HSF-1 overexpression, HSB-1 inhibition alters the expression of less than 500 genes in C. elegans. Roughly half of the differentially regulated transcripts in the hsb-1 mutant have altered expression also in hsf-1 overexpressing animals, with a strongly correlated fold-expression pattern between the two strains. In addition, genes that are upregulated via both HSB-1 inhibition and HSF-1 overexpression include numerous DAF-16 targets that have known functions in longevity regulation. This study identifies how HSB-1 acts as a specific regulator of the transactivation potential of HSF-1 in non-stressed conditions, thus providing a detailed understanding of the role of HSB-1/HSF-1 signaling pathway in transcriptional regulation and longevity in C. elegans.

genetics↗