Biology subjects

Ji, J.-y.

Publications and source records attributed to Ji, J.-y..

6 recordsLinked to original sources

bioRxiv2026

Developmental patterning of adipose tissue by abd-A and Abd-B homeotic genes in Drosophila melanogaster

The Bithorax Complex (BX-C) homeobox proteins specify segmental identities along the anterior-posterior axis during Drosophila embryogenesis. Differential expression of the BX-C genes abd-A and Abd-B distinguishes abdominal from thoracic adipocytes, yet the mechanism regulating this heterogeneity remains poorly understood. Here, we identify cis-regulatory elements (CREs) and transcription factors that direct abdominal-specific expression of abd-A and Abd-B in the larval fat body. Fine-mapping analyses identified a 627-bp CRE within the Abd-B locus and a [~]6-kb CRE within the abd-A locus sufficient to drive heterogeneous expression. Yeast one-hybrid screening combined with functional analyses identified Lola, Lolal, and Combgap as key repressors of Abd-B, whereas Piragua (Prg) and Seven up (Svp) function as transcriptional activators, indicating that adipocyte heterogeneity in postembryonic adipose tissue is actively regulated. In turn, lola and prg are repressed by Abd-B, whereas lolal and svp are activated, forming a feedback circuit further modulated by Wnt signaling, which promotes lola and lolal expression while repressing svp. CUT&RUN analyses suggest that these interactions are direct, with dTCF/Pan and Abd-B occupancy detected at target loci. Together, our findings define a transcriptional circuit that regulates Abd-B gene transcription to pattern adipose tissue and may establish the developmental basis of fat depot specialization. One-sentence summaryTranscriptional regulation of abd-A & Abd-B in adipocytes

genetics↗

bioRxiv2024

Metabolic control by the Bithorax Complex-Wnt signaling crosstalk in Drosophila

Adipocytes distributed throughout the body play crucial roles in lipid metabolism and energy homeostasis. Regional differences among adipocytes influence normal function and disease susceptibility, but the mechanisms driving this regional heterogeneity remain poorly understood. Here, we report a genetic crosstalk between the Bithorax Complex (BX-C) genes and Wnt/Wingless signaling that orchestrates regional differences among adipocytes in Drosophila larvae. Abdominal adipocytes, characterized by the exclusive expression of abdominal A (abd-A) and Abdominal B (Abd-B), exhibit distinct features compared to thoracic adipocytes, with Wnt signaling further amplifying these disparities. Depletion of BX-C genes in adipocytes reduces fat accumulation, delays larval-pupal transition, and eventually leads to pupal lethality. Depleting Abd-A or Abd-B reduces Wnt target gene expression, thereby attenuating Wnt signaling-induced lipid mobilization. Conversely, Wnt signaling stimulated abd-A transcription, suggesting a feedforward loop that amplifies the interplay between Wnt signaling and BX-C in adipocytes. These findings elucidate how the crosstalk between cell-autonomous BX-C gene expression and Wnt signaling define unique metabolic behaviors in adipocytes in different anatomical regions of fat body, delineating larval adipose tissue domains.

developmental biology↗

bioRxiv2024

Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila

The Mediator complex, composed of about 30 conserved subunits, plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising Med12, Med13, CDK8, and CycC (Cyclin C), serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes of CDK8-CycC and Med12-Med13 mutations, yet the underlying mechanism has remained unknown. Here, using Drosophila as a model organism, we show that depleting CDK8-CycC enhances E2F1 target gene expression and promotes cell-cycle progression. Conversely, depletion of Med12-Med13 affects the expression of ribosomal protein genes and fibrillarin, indicating a more severe reduction in ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Moreover, we found that the stability of CDK8 and CycC relies on Med12 and Med13, with a mutually interdependent relationship between Med12 and Med13. Furthermore, CycC stability depends on the other three CKM subunits. These findings reveal distinct roles for CKM subunits in vivo, with Med12-Med13 disruption exerting a more pronounced impact on ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. SignificanceThe CDK8 kinase module (CKM), comprising CDK8, CycC, Med12, and Med13, is essential in the Mediator complex for RNA polymerase II-dependent transcription in eukaryotes. While expected to function jointly, CKM subunit mutations result in distinct phenotypes in Drosophila. This study investigates the mechanisms driving these differing effects. Our analysis reveals the role of Med12-Med13 pair in regulating ribosomal biogenesis and cellular growth, contrasting with the involvement of CDK8-CycC in E2F1-dependent cell-cycle progression. Additionally, an asymmetric interdependence in the stability of CDK8-CycC and Med12-Med13 was observed. CKM mutations or overexpression are associated with cancers and cardiovascular diseases. Our findings underscore the distinct impacts of CKM mutations on cellular growth and proliferation, advancing our understanding of their diverse consequences in vivo.

cell biology↗

bioRxiv2023

Transcriptional coupling of telomeric retrotransposons with the cell cycle

Instead of employing telomerases to safeguard chromosome ends, dipteran species maintain their telomeres by transposition of telomeric-specific retrotransposons (TRs): in Drosophila, these are HeT-A, TART, and TAHRE. Previous studies have shown how these TRs create tandem repeats at chromosome ends, but the exact mechanism controlling TR transcription has remained unclear. Here we report the identification of multiple subunits of the transcription cofactor Mediator complex and transcriptional factors Scalloped (Sd, the TEAD homolog in flies) and E2F1-Dp as novel regulators of TR transcription and telomere length in Drosophila. Depletion of multiple Mediator subunits, Dp, or Sd increased TR expression and telomere length, while over-expressing E2F1-Dp or knocking down the E2F1 regulator Rbf1 (Retinoblastoma-family protein 1) stimulated TR transcription, with Mediator and Sd affecting TR expression through E2F1-Dp. The CUT&RUN analysis revealed direct binding of CDK8, Dp, and Sd to telomeric repeats. These findings highlight the essential role of the Mediator complex in maintaining telomere homeostasis by regulating TR transcription through E2F1-Dp and Sd, revealing the intricate coupling of TR transcription with the host cell-cycle machinery, thereby ensuring chromosome end protection and genomic stability during cell division.

cell biology↗

bioRxiv2023

Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression

Conserved Wnt/Wingless signaling plays pivotal roles in regulating normal development and energy metabolism in metazoans, and aberrant activation of Wnt signaling drives the pathogenesis of many diseases including cancer. However, the role of Wnt signaling in regulating cellular lipid homeostasis, particularly lipid mobilization, remains poorly understood. Here we show that canonical Wg signaling inhibits lipid accumulation in Drosophila larval adipocytes by stimulating lipid catabolism while simultaneously inhibiting lipogenesis. Using a combination of RNA-sequencing and CUT&RUN assays, we identified a battery of Wg target genes encoding key factors required for lipogenesis (such as FASN1 and AcCoS), lipolysis (such as lipid droplet-associated proteins Lsd-1 and Lsd-2), and fatty acid {beta}-oxidation in the mitochondria and peroxisome (e.g., CPT1 and CRAT), most of which are directly repressed by active Wg signaling. Furthermore, lipid accumulation defects caused by active Wg signaling are rescued by either ectopically expressing Lsd-1 and Lsd-2 or depleting the transcriptional repressor Aef1, whose binding motif was identified in 52% of Wg signaling-repressed genes. These findings suggest that active Wg signaling reduces intracellular lipid accumulation by inhibiting lipogenesis and fatty acid {beta}-oxidation and by promoting lipolysis and lipid mobilization, and Wg signaling-induced transcriptional repression play a prominent role in these converging mechanisms.

cell biology↗

bioRxiv2019

Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus

Systemic lupus erythematosus (SLE), characterized by chronic inflammation and multi-organ damage, has been suggested to associate with gut dysbiosis, but knowledge is limited from small sample size and 16s rRNA-based studies. To shed new light on the role of microbiota in SLE development, we analyzed the fecal metagenome of 117 treatment-naive SLE patients and 115 sex- and age-matched healthy controls (HC) by deep-sequencing; in addition, 52 of the aforementioned patients have post-treatment fecal metagenome for comparison. We found significant differences in microbial composition and function between SLE and HC, revealing multiple plausible contributing bacterial species and metabolic pathways in SLE. In-depth SNP-based analysis revealed an oral-microbiome origin for two marker species, strengthening the importance of bacterial translocation in disease development. Lastly, we confirmed experimentally that peptides of SLE-enriched species mimicking autoantigens such as Sm and Fas could trigger autoimmune responses, suggesting a potential causal role of gut microbiota in SLE.

microbiology↗