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Chromatin conformation dynamics during CD4+ Tcell activation implicates autoimmune disease associated genes and regulatory elements (HiC)

ABSTRACT: We used ATAC-seq, RNA-seq, and HiC to create atlases of the regulatory elements to provide context to autoimmune disease associated variants from publically available Genome-wide association studies

ORGANISM(S): Homo sapiens

PROVIDER: GSE230342 | GEO | 2024/09/18

REPOSITORIES: GEO

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Chromatin conformation dynamics during CD4+ Tcell activation implicates autoimmune disease associated genes and regulatory elements (RNA-Seq)

Project description:We used ATAC-seq, RNA-seq, and HiC to create atlases of the regulatory elements to provide context to autoimmune disease associated variants from publically available Genome-wide association studies

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Chromatin conformation dynamics during CD4+ Tcell activation implicates autoimmune disease associated genes and regulatory elements (ATAC-Seq)

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Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C [RNA-Seq]

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Selective enhancement and repression of glucocorticoid receptor signaling by coregulator Hic-5

Project description:The glucocorticoid receptor (GR) recruits many coregulators via the well characterized AF2 interaction surface in the GR ligand binding domain, but LIM domain coregulator Hic-5 binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of Hic-5 for glucocorticoid-regulated gene expression in U2OS osteosarcoma cells was defined by Hic-5 depletion and global gene expression analysis. Hic-5 depletion had selective and dramatic effects, positive and negative, on both activation and repression of GR target genes. For some hormone-induced genes, Hic-5 facilitated recruitment of the Mediator complex and RNA polymerase II. In contrast, many genes were not regulated by hormone until Hic-5 was depleted. On these genes Hic-5 acted at a very early step of the regulatory process, preventing efficient GR binding on enhancers, chromatin remodeling, and thus preventing glucocorticoid-driven transcriptional regulation. Overall, Hic-5 has selective and diverse roles on GR target genes, functioning as coactivator on some genes and corepressor on others, and either facilitating or opposing the glucocorticoid-driven actions of GR. Hic-5 exhibits multiple mechanisms of action, either regulating GR binding to DNA and chromatin remodeling, or facilitating later steps in transcription complex assembly. We investigate the relationship between GR and Hic5 and identify classes of genes that respond differently when cells are induced with hormone and when Hic5 is knocked down We knock down Hic-5 (TGFB1I1) in U2OS cells using siRNA (siHic5_2) along with nonspecific siRNA (shNS) and assay gene expression changes at 4 different time points of hormone treatment. We also include non-infected control (NI) as a second control at each time point.

2014-03-21 | E-GEOD-46448 | biostudies-arrayexpress

Chromosome conformation analysis of N1E115 cells by HiC

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Chromatin conformation dynamics during CD4+ T cell activation implicates 2 autoimmune disease-associated genes and regulatory elements

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-18 | GSE230346 | GEO

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2023-02-20 | E-MTAB-12664 | biostudies-arrayexpress

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