Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE151013 | GEO | 2021/08/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [RNA-seq]

Project description:Using mouse models of several recessive and putative dominant-negative patient mutations we were able to dissect the mechanisms that underlie the recessive and dominant-negative capacities of the corresponding AIRE mutants, including a newly identified dominant-negative variant C446G We also identify an auto-regulatory mechanism by which AIRE negatively modulates its own expression.

2021-09-01 | GSE151012 | GEO

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [ATAC-seq]

2021-09-01 | GSE151011 | GEO

Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE auto-regulation [ChIP-Seq]

2021-09-01 | GSE165550 | GEO

Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation.

Project description:The autoimmune regulator (AIRE) is essential for the establishment of central tolerance and prevention of autoimmunity. Interestingly, different AIRE mutations cause autoimmunity in either recessive or dominant-negative manners. Using engineered mouse models, we establish that some monoallelic mutants, including C311Y and C446G, cause breakdown of central tolerance. By using RNAseq, ATACseq, ChIPseq, and protein analyses, we dissect the underlying mechanisms for their dominancy. Specifically, we show that recessive mutations result in a lack of AIRE protein expression, while the dominant mutations in both PHD domains augment the expression of dysfunctional AIRE with altered capacity to bind chromatin and induce gene expression. Finally, we demonstrate that enhanced AIRE expression is partially due to increased chromatin accessibility of the AIRE proximal enhancer, which serves as a docking site for AIRE binding. Therefore, our data not only elucidate why some AIRE mutations are recessive while others dominant, but also identify an autoregulatory mechanism by which AIRE negatively modulates its own expression.

| S-EPMC8421262 | biostudies-literature

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation

Project description:Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation

| PRJNA634367 | ENA

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [ATAC-seq]

Project description:Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [ATAC-seq]

| PRJNA634368 | ENA

Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [RNA-seq]

Project description:Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [RNA-seq]

| PRJNA634369 | ENA

Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE auto-regulation [ChIP-Seq]

Project description:Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE auto-regulation [ChIP-Seq]

| PRJNA694945 | ENA

Models of aire-dependent gene regulation for thymic negative selection.

Project description:Mutations in the autoimmune regulator (AIRE) gene lead to autoimmune polyendocrinopathy syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue-restricted antigens (TRAs) in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

| S-EPMC3342030 | biostudies-literature

Exome Sequencing Reveals Mutations in AIRE as a Cause of Isolated Hypoparathyroidism.

Project description:ContextMost cases of autosomal recessive hypoparathyroidism (HYPO) are caused by loss-of-function mutations in GCM2 or PTH.ObjectiveThe objective of this study was to identify the underlying genetic basis for isolated HYPO in a kindred in which 3 of 10 siblings were affected.SubjectsWe studied the parents and the three adult affected subjects, each of whom was diagnosed with HYPO in the first decade of life.MethodsWe collected clinical and biochemical data and performed whole exome sequencing analysis on DNA from the three affected subjects after negative genetic testing for known causes of HYPO.ResultsWhole exome sequencing followed by Sanger sequencing revealed that all three affected subjects were compound heterozygous for two previously reported mutations, c.967_979delCTGTCCCCTCCGC:p.(L323SfsX51) and c.995+(3_5)delGAGinsTAT, in AIRE, which encodes the autoimmune regulator protein that is defective in autoimmune polyglandular syndrome type 1 (APS-1). Each parent carries one mutation, and all of the children of the patients are either heterozygous for one mutation or wild type. The affected sister developed premature ovarian failure, but the two affected brothers have no other features of APS-1 despite elevated serum levels of anti-interferon-α antibodies.ConclusionsOur findings indicate that biallelic mutations in AIRE can cause isolated HYPO as well as syndromic APS-1. The presence of antibodies to interferon-α provides a highly sensitive indicator for loss of AIRE function and represents a useful marker for isolated HYPO due to AIRE mutations.

| S-EPMC5443324 | biostudies-literature

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