Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping

ABSTRACT: An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping

PROVIDER: PRJNA705948 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13826560_1.fastq.gz	Fastqsanger.gz
	SRR13826560_2.fastq.gz	Fastqsanger.gz
	SRR13826562_1.fastq.gz	Fastqsanger.gz
	SRR13826562_2.fastq.gz	Fastqsanger.gz
	SRR13826563_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping

Project description:Genetic sharing is extensively observed for many autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of known autoimmune disease pleiotropic loci, we found that most of these genetic effects are transmitted from regulatory code and colocalize with hematopoietic lineage-specific expression quantitative trait loci. We used an evidence-based strategy to functionally prioritize known pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal, and regulates IRF5 transcript expression. Mechanistically, the rs4728142-containing region interacts with the IRF5 downstream alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific chromatin looping to promote IRF5 short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.

2021-03-03 | GSE168045 | GEO

An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.

Project description:Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.

| S-EPMC9984425 | biostudies-literature

Genome-wide maps of chromatin state of IRF5+/+ and IRF5-/- CD4+ mouse T cells

Project description:Genetic variants in IRF5 are associated with multiple immune-mediated diseases. IRF5 has been predominantly focused on for its regulation of myeloid-derived cells. We found that IRF5 contributes to CD4+ T cell outcomes and that it regulates early T cell receptor-initiated signaling and subsequently translocates to the nucleus where it binds to promoters of various genes regulated with T cell activation. We report the chromatin state of freshly isolated and activated IRF5+/+ and IRF5-/- CD4+ T cells in vitro. While there are minimal differential peaks between freshly isolated IRF5+/+ and IRF5-/- CD4+ T cells, once activated multiple differential peaks are observed between IRF5+/+ and IRF5-/- CD4+ T cells.

2020-06-29 | GSE148672 | GEO

RNA-sequencing of IRF5+ and IRF5- circulating monocytes from patients with Type-2 Diabetes

Project description:Purpose: To characterise the transcriptomic landscape in monocytes associated with IRF5 expression Methods: RNA sequencing from FACS sorted IRF5+ and IRF5- CD14+ monocytes Results: Differential expression based on IRF5 postiivity provides insight into its roles in monocyte function and in type-2 diabetes Conclusions: This study represents the first analyses of IRF5-dependent transcriptome in circulating monocytes from patients with Type-2 diabetes

2022-07-22 | GSE176216 | GEO

Expression analysis of murine splenic B-cells after retroviral transduction with a constitutively active variant of IRF5 (IRF5-4D)

Project description:Genome-wide gene expression analysis of murine splenic B-cells following retroviral transduction with a constitutively active IRF5 (IRF5-4D) Illumina WG-6 v2.0 arrays were hybridized to determine the gene expression profile of murine splenic B-cells following retroviral transduction with i) control virus (MSCV-IRES-CFP) or ii) IRF5-4D virus (MSCV-IRF5-4D-CFP). All hybridizations were done in biological triplicates.

2014-09-24 | E-GEOD-51719 | biostudies-arrayexpress

Gene expression profiling in wild-type, Irf5-KO, Lyn-KO and Lyn/Irf5-DKO BMDCs unstimulated or stimulated with CpG-B ODN

Project description:To characterize the relationship between IRF5 and Lyn in innate immune responses at a genome-wide scale, we performed gene expression microarray analysis for wild-type (WT), Irf5-KO, Lyn-KO and Lyn/Irf5-DKO bone marrow-derived dendritic cells (BMDCs) with or without 6 h-stimulation with 150 nM CpG-B ODN. We extracted the transcripts that were upregulated by CpG-B ODN in WT BMDCs, further upregulated in Lyn-KO BMDCs and then downregulated in Lyn/Irf5-DKO BMDCs (fold change â?¥ 2, false discovery rate < 0.05). When these 79 transcripts were sorted by their expression levels in Lyn-KO BMDCs, most of the top 20 genes (13 out of 20) were those encoding type I interferons (IFNs), indicating that Lyn particularly suppresses IRF5 induction of type I IFNs. BMDCs from WT, Irf5-KO, Lyn-KO and Lyn/Irf5-DKO mice in a C57BL/6 background were unstimulated or stimulated with CpG-B ODN. Biological triplicate for each genotype were analyzed (24 samples in total).

2016-07-25 | E-GEOD-63014 | biostudies-arrayexpress

Expression analysis of Reh cells after transfection with constitutively active variants of IRF5 (IRF5-4D) and/or constitutively active IKKÎ²(EE)

Project description:Genome-wide gene expression analysis of Reh cells following transfection with constitutively active IRF5-4D, constitutively active IKKÎ²(EE), or both in combination. Affymetrix U133 Plus 2.0 oligonucleotide arrays were hybridized to determine the gene expression profile of acute lymphoblastic leukemia-derived Reh cells following transfection with i) control constructs, ii), a constitutively active variant of IRF5 (IRF5-4D), iii) a constitutively active variant of the IkB kinase Î² (IKKÎ²(EE)), or iv) IRF5-4D in combination with IKKÎ²(EE). All hybridizations were done in biological duplicates.

2014-09-24 | E-GEOD-51717 | biostudies-arrayexpress

Expression analysis of murine splenic B-cells after retroviral transduction with a constitutively active variant of IRF5 (IRF5-4D)

Project description:Genome-wide gene expression analysis of murine splenic B-cells following retroviral transduction with a constitutively active IRF5 (IRF5-4D)

2014-09-24 | GSE51719 | GEO

Gene expression profiling in wild-type, Irf5-KO, Lyn-KO and Lyn/Irf5-DKO BMDCs unstimulated or stimulated with CpG-B ODN

Project description:To characterize the relationship between IRF5 and Lyn in innate immune responses at a genome-wide scale, we performed gene expression microarray analysis for wild-type (WT), Irf5-KO, Lyn-KO and Lyn/Irf5-DKO bone marrow-derived dendritic cells (BMDCs) with or without 6 h-stimulation with 150 nM CpG-B ODN. We extracted the transcripts that were upregulated by CpG-B ODN in WT BMDCs, further upregulated in Lyn-KO BMDCs and then downregulated in Lyn/Irf5-DKO BMDCs (fold change ≥ 2, false discovery rate < 0.05). When these 79 transcripts were sorted by their expression levels in Lyn-KO BMDCs, most of the top 20 genes (13 out of 20) were those encoding type I interferons (IFNs), indicating that Lyn particularly suppresses IRF5 induction of type I IFNs.

2016-07-25 | GSE63014 | GEO

IRF5 and IRF3 regulate distinct immune programs in plasmacytoid dendritic cells

Project description:Transcriptomic analyses of pDCs show that the partitioning of TLR/IRF5 and RLR/IRF3 pathways confers differential gene expression and immune cytokine production in pDCs, linking IRF5 with immune regulatory and proinflammatory gene expression.

2017-12-27 | GSE108526 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data