GSE56240 | Datasets2Tools

General Information

Accession	GSE56240
Title	Chemical Inhibition of the RORt-dependent Transcriptional Network in Th17 cells [RNA-Seq 2]
Description	RORt is a transcription factor required for T helper 17 (Th17) cell development. We identified three RORt-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized RORt binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and RORt-deficient cells. RORt is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced RORt from its target-loci, the two more potent inhibitors affected transcription predominantly without removing DNA-binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity.
Landing Page	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56240
Repository	Gene Expression Omnibus