Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing of cells derived from the site of inflammation of Juvenile Idiopathic Arthritis patients

ABSTRACT: Through RNA sequencing of CD4+ Tmemory/effector cells derived from the synovium of JIA patients and healthy controls, we analyzed the JIA gene expression signature. Treatment of autoinflammatory site-derived patient T cells with the BET-inhibitor JQ1 inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. RNA-sequencing of CD4+ memory/effector T cells derived from Healthy Controls (HC) and JIA patients upon JQ1 treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Janneke Peeters

PROVIDER: E-GEOD-71595 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

Peeters Janneke G C JG Vervoort Stephin J SJ Tan Sander C SC Mijnheer Gerdien G de Roock Sytze S Vastert Sebastiaan J SJ Nieuwenhuis Edward E S EE van Wijk Femke F Prakken Berent J BJ Creyghton Menno P MP Coffer Paul J PJ Mokry Michal M van Loosdregt Jorg J

Cell reports 20150917 12

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, i ...[more]

PMID: 26387944

Similar Datasets

Epigenetic profiling of Juvenile Idiopathic Arthritits (JIA) patients

Project description:With H3K27ac chromatin immunoprecipitation we identified a disease-specific, inflammation-associated, (super-)enhancer signature in JIA patient synovial fluid-derived CD4+ memory/effector T cells. This signature consists of unique pathogenesis-associated epigenetic changes which extend beyond general T cell activation-induced alterations, indicating that disease-specific (super-)enhancers contribute to JIA pathogenesis. In addition, our analysis shows that there is a profound enrichment of JIA-related SNPs in (super-)enhancers in JIA patients compared to controls, illustrating the importance of these non-coding regions for disease pathogenesis. H3K27ac ChIP-sequencing of CD4+ memory/effector T cells derived from peripheral blood (PB) from healthy controls (HC) and PB or synovial fluid (SF) from JIA patients.

2015-09-15 | E-GEOD-71596 | biostudies-arrayexpress

RNA-sequencing of cells derived from the site of inflammation of Juvenile Idiopathic Arthritis patients

Project description:Through RNA sequencing of CD4+ Tmemory/effector cells derived from the synovium of JIA patients and healthy controls, we analyzed the JIA gene expression signature. Treatment of autoinflammatory site-derived patient T cells with the BET-inhibitor JQ1 inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes.

2015-09-15 | GSE71595 | GEO

Proteome of neutrophils upon migration towards inflamed synovial fluid

Project description:Analysis of neutrophil proteomic alterations induced by migration towards inflamed joints in juvenile idiopathic arthritis (JIA). In this experiment neutrophil proteomes were investigated after migration towards JIA synovial fluid in an in vitro model of a synovial membrane, compared to neutrophils incubated in synovial fluid without migration. The migration model consisted of transwell inserts with human knee synoviocytes on the undersides and HMEC endothelial cells on the insides, placed in wells containing medium with 10 % JIA synovial fluid.

2022-02-15 | PXD029129 | Pride

Multiplexed proteome dynamics profiling of JQ1-PROTAC

Project description:Goal of this experiment was the differentiation of direct targets of induced degradation of the JQ1-PROTAC from downstream regulatory effects.

2018-05-02 | PXD008637 | Pride

RNA-seq of L3.6pl cells treated with CI994, TW9, and CI994 + JQ1

Project description:Evaluation of gene expression profiles upon treatment with CI994, TW9, and CI994 + JQ1 for 24 hours treatment

2023-08-17 | E-MTAB-7214 | biostudies-arrayexpress

Epigenetic profiling of Juvenile Idiopathic Arthritits (JIA) patients

2015-09-15 | GSE71596 | GEO

High Resolution Mapping of RNA Polymerases Identifies Mechanisms of Sensitivity and Resistance to BET Inhibitors in t(8;21) AML

Project description:Bromodomain and extra-terminal domain (BET) family inhibitors offer a new approach to treating hematological malignancies. We used precision nuclear run-on transcription sequencing (PRO-seq) to create high-resolution maps of active RNA polymerases across the genome in t(8;21) acute myeloid leukemia (AML) that are exceptionally sensitive to BET inhibitors. PRO-seq identified over 1400 genes showing impaired release of promoter-proximal paused RNA polymerases, including the stem cell factor receptor tyrosine kinase KIT that is mutated in t(8;21) AML. PRO-seq also identified an enhancer 3â to KIT. Chromosome conformation capture confirmed contacts between this enhancer and the KIT promoter and CRISPRi-mediated repression of this enhancer impaired cell growth. PRO-seq also identified microRNAs, including MIR29C and MIR29B2 that target the anti-apoptotic factor MCL1 and were repressed by BET inhibitors. MCL1 protein was up-regulated, and inhibition of BET proteins sensitized t(8:21)-containing cells to MCL1 inhibition, suggesting a potential mechanism of resistance to BET inhibitor-induced cell death. Kasumi-1 cells were treated with DMSO, 250 nM JQ1, and 125 nM MS417 for 1 and 3 hours, and PRO-seq was performed to study transcriptional changes. Kasumi-1 cells were treated with 250 nM JQ1 for 0, 15, and 30 minutes, and PRO-seq was performed. Two biological replicates were included for each time point. Primary AML patient cells were treated with DMSO and 250 nM JQ1 for 1 hour, and PRO-seq was performed to confirm trancriptional effects of BET inhibitors.

2016-07-15 | E-GEOD-83660 | biostudies-arrayexpress

Thermal proteome profiling of JQ1

Project description:Goal of this experiment was the identification of proteins affected in their thermal stability by JQ1.

2018-05-02 | PXD008638 | Pride

Bromodomain-Containing-Protein 4 (BRD4) Regulates RNA Polymerase II Serine 2 Phosphorylation in Human CD4+ T Cells

Project description:Transcriptional elongation by RNA polymerase II (Pol II) is regulated by positive transcription elongation factor b (P-TEFb) in association with Bromodomain-containing protein 4 (BRD4). We used genome-wide chromatin immunoprecipitation sequencing in primary human CD4+ T cells to reveal that BRD4 co-localizes with Ser2-phosphorylated Pol II (Pol II Ser2) at both enhancers and promoters of active genes. Disruption of bromodomain:histone acetylation interactions by JQ1, a small-molecule bromodomain inhibitor, resulted in decreased BRD4 binding, reduced Pol II Ser2, and reduced expression of lineage-specific genes in primary human CD4+ T cells. A large number of JQ1-disrupted BRD4 binding regions exhibited di-acetylated H4 (lysine-5 and -8) and H3K27 acetylation (H3K27ac), which correlated with the presence of histone acetyltransferases and deacetylases. Genes associated with BRD4/H3K27ac co-occupancy exhibited significantly higher activity than those associated with H3K27ac or BRD4 binding alone. Comparison of BRD4 binding in T cells and in human embryonic stem cells revealed that enhancer BRD4 binding sites were predominantly lineage-specific. Our findings suggest that BRD4-driven Pol II phosphorylation at serine 2 plays an important role in regulating lineage-specific gene transcription in human CD4+ T cells. Examination of BRD4, total Pol II, serine 2 phosphorylated Pol II and serine 5 phosphorylated Pol II binding in CD4+ T cells (with and without JQ1 treatment) and BRD4 binding in human embryonic stems cell; PolyA RNA expression in CD4+ T cells( with and without JQ1 treatment) using RNA-seq

2012-11-14 | E-GEOD-33281 | biostudies-arrayexpress

2 Dimensional Thermal proteome profiling of JQ1

Project description:Goal of this experiment was the identification of proteins affected dose dependently in their thermal stability by JQ1.

2018-05-02 | PXD008626 | Pride