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Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1

ABSTRACT: Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1

PROVIDER: PRJNA397973 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5927240_1.fastq.gz	Fastqsanger.gz
	SRR5927240_2.fastq.gz	Fastqsanger.gz
	SRR5927241_1.fastq.gz	Fastqsanger.gz
	SRR5927241_2.fastq.gz	Fastqsanger.gz
	SRR5927242_1.fastq.gz	Fastqsanger.gz

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Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1 [Affymetrix]

Project description:Gene Expression Profiles of mTECs from Aire-/- and Brg1-/- mice and their littermate controls.

2017-12-13 | GSE102525 | GEO

Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1 [ATAC-Seq]

Project description:Chromatin Accessibility Profiles of mTECs from Aire-/- and Brg1-/- mice and their littermate controls.

2017-12-06 | GSE102526 | GEO

Differential features of Aire-induced and Aire-independent promiscuous gene expression in thymic epithelial cells

Project description:Promiscuous gene expression (pGE) of numerous self-antigens in thymic epithelial cells (TEC) enables the elimination of self-reactive T cells. The autoimmune regulator (Aire) is the only known molecular determinant driving pGE in the thymus but the existence of Aire-independent mechanisms has been inferred. Here, we analyzed the poly(A)+ transcriptome of TEC populations by RNA-sequencing (RNA-seq) in order to reveal differential features of Aire-induced vs. –independent pGE. We report an unanticipated effect of Aire deletion on the proliferation and differentiation of cortical TEC. Moreover, the RNA-seq data reveal the breath of Aire-induced and –independent pGE in medullary TEC (mTEC) subsets and the extent of thymic peripheral tissue representation. The results suggest that Aire-induced promiscuously expressed transcripts affect several functions with far reaching biological consequences in mTEC. High-throughput characterization of TEC transcriptomes will enable progress in understanding TEC biology and the establishment of self-tolerance. The mRNA profiles of cTEC, mTEClo and mTEChi from 6-8 week-old wild type (WT) and Aire-/- (KO) mice were generated by RNA-sequencing using Illumina HiSeq2000.

2015-05-19 | E-GEOD-65617 | biostudies-arrayexpress

Differential features of Aire-induced and Aire-independent promiscuous gene expression in thymic epithelial cells

2015-05-19 | GSE65617 | GEO

Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1

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

2017-12-06 | GSE102527 | GEO

Mus musculus

Project description:Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1 [Affymetrix]

| PRJNA397971 | ENA

Transcriptional regulation by Aire in medullary thymic epithelial cells revisited

Project description:The deficiency of Aire, a transcriptional regulator whose defect results in the development of autoimmunity, is associated with reduced expression of tissue-restricted self-Ags (TRAs) in medullary thymic epithelial cells (mTECs). Although the mechanisms underlying Aire-dependent expression of TRAs need to be explored, the physical identification of the target(s) of Aire has been hampered by the low and promiscuous expression of TRAs. We have tackled this issue by engineering mice with augmented Aire expression. Integration of the transcriptomic data from Aire-augmented and Aire-deficient mTECs revealed that a large proportion of so-called Aire-dependent genes, including those of TRAs, may not be direct transcriptional targets downstream of Aire. Rather, Aire induces TRA expression indirectly through controlling the heterogeneity of mTECs, as revealed by single-cell analyses. In contrast, Ccl25 emerged as a canonical target of Aire, and we verified this both in vitro and in vivo. Our approach has illuminated the Aire?s primary targets while distinguishing them from the secondary targets.

2021-10-13 | GSE155331 | GEO

Mus musculus

Project description:Rheostatic Chromatin Control of Promiscuous Transcription by Aire and Brg1 [ATAC-Seq]

| PRJNA397970 | ENA

Expression data from WT and Aire deficient mTECs

Project description:Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED. Keywords: Gene expression comparison between genotypes In this experiment there are 5 samples altogether which consist of two biological replicates of Aire knock-out mTECs and 3 biological replicates of wild type mTECs.

2009-03-15 | E-GEOD-14365 | biostudies-arrayexpress

Sirt1 is essential for Aire-mediated induction of central immunological tolerance

Project description:Autoimmune regulator (Aire) is a unique transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for induction of immunological self-tolerance. Although several recent studies provided very important molecular insights into how Aire operates, a more comprehensive understanding of this process still remains elusive. Here we demonstrate that a lysine deacetylase Sirtuin-1 (Sirt1) is predominantly expressed in mature Aire+ mTECs, where it is required for expression of Aire-dependent TRA genes and a subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and uncovers a unique functional role for Sirt1 in preventing organ-specific autoimmunity.

2015-05-25 | GSE68190 | GEO

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