Project description:ChIP-seq profiles for CTCF and TGF-beta signaling factors before and after treatment with DPP Examination of transcription factor dynamics during signaling
Project description:The dorsal patterning in Drosophila is controlled by an extracellular gradient of the morphogens Decapentlaplegic/Screw (Dpp/Scrw), which are members of BMP/TGF-β family. Dpp/Scrw signal is transduced to the nucleus by the transcription factors, Mad/Medea. The transcriptional effectors exert their regulation in a graded-manner eliciting at least three threshold responses: high, intermediate and low. However, the mechanism underlying differential response to Dpp is poorly understood, due in part to the insufficient number of well-studied target genes. Gene expression changes were analysed in ectopic overexpressing Dpp mutant embryos to identify new target genes of Dpp/Mad pathway.
Project description:Wnt/beta-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. The results of the present studies suggest that Wnt signaling is interacting with TGF-beta superfamily signaling through Smad activation. Single analysis for each condition (proliferating C2C12 cells, differentiating C2C12 cells, proliferating Wnt4-overexpressing C2C12 subline cells).
Project description:Our study shows that TGF-β signaling promotes tumorigenesis in the liver through upregulation of its target gene, Snail. We explored gene expression changes in tumors following TGF-β inhibition, and tumors ectopically expressing Snail with the TGF-β inhibition. RNA samples were harvested from tumors expressing Smad7 (S7HP tumors), firefly luciferase (LHP tumors), and Smad7 plus Snail (S7HP+Snail), respectively. Differentially expressed genes were investigated in LHP and S7HP+Snail tumors, compared with S7HP tumors.
Project description:The goal of the current study was to examine the extent to which TGF-beta signaling contributes to insulin-induced transcriptional responses in endothelial cells (HUVECs). HUVECs cells were treated with or without insulin in the absence or presence of SB431542, a TGF-beta receptor kinase inhibitor. Cells were sequenced using Hiseq 2000 (Illumina) as paired-end 2x100 base reads.
Project description:We sought to explore whether BAF45D regulates PAX6 expression through cooperating with TGF-beta/SMAD signaling in RA treated P19 cells. Here we identified BAF45D is required for expression of phosphorylated SMAD3 and PAX6 induced by RA. Genome-wide analysis revealed that during RA-induced early neural differentiation, BAF45D knockdown failed to activate TGF-beta/SMAD signaling and induce expression of Stat3 and Smad7, two negative regulators of TGF-beta/SMAD signaling. Moreover, BAF45D was immunoprecipited with BRG1and phosphorylated SMAD3. In addition, Smad3 siRNA abolished RA-indueced expression of phosphorylated SMAD3, PAX6, STAT3 and SMAD7. Finally, overexpression of BAF45D directly induced expression of PAX6 and phosphorylated SMAD3.These results suggest that a novel effect of BAF45D cooperating with TGF-beta/SMAD signaling pathway on PAX6 level control, which may shed new light on neural differentiation of P19 cells.
Project description:In animals, the brain regulates feeding behavior in response to local energy demands of peripheral tissues, which secrete orexigenic and anorexigenic hormones. Although skeletal muscle is a key peripheral tissue, it remains unknown whether muscle-secreted hormones regulate feeding. In Drosophila , we find that decapentaplegic (dpp), the homolog of human bone morphogenetic proteins BMP2 and BMP4, is a muscle-secreted factor (a myokine) that is induced by nutrient sensing and that circulates and signals to the brain. Muscle-restricted dpp RNAi promotes foraging and feeding initiation whereas dpp overexpression reduces it. This regulation of feeding by muscle-derived Dpp stems from modulation of brain tyrosine hydroxylase (TH) expression and dopamine biosynthesis. Consistently, Dpp receptor signaling in dopaminergic neurons regulates TH expression and feeding initiation via the downstream transcriptional repressor Schnurri. Moreover, pharmacologic modulation of TH activity rescues the changes in feeding initiation due to modulation of dpp expression in muscle. These findings indicate that muscle-to-brain endocrine signaling mediated by the myokine Dpp regulates feeding behavior.
Project description:Wnt/beta-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. The results of the present studies suggest that Wnt signaling is interacting with TGF-beta superfamily signaling through Smad activation.