Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA299575 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2754990.fastq.gz | Fastqsanger.gz | |||
| SRR2755000.fastq.gz | Fastqsanger.gz | |||
| SRR2754991.fastq.gz | Fastqsanger.gz | |||
| SRR2755001.fastq.gz | Fastqsanger.gz | |||
| SRR2754992.fastq.gz | Fastqsanger.gz |
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Project description:Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. We used sequence conservation analysis and ChIP-seq against the enhancer-associated histone mark H3K27ac to identify a candidate Aire cis-regulatory element. There is enrichment of H3K27ac near this element, ACNS1, in mTECs and the element also has characteristics of being NF-κB-responsive. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance. Two experimental groups (GFP neg mTECs and GFP pos mTECs), each with three samples, and one control sample (D10 Th2 cells).
2015-10-23 | E-GEOD-74257 | biostudies-arrayexpress
Project description:Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. We used sequence conservation analysis and ChIP-seq against the enhancer-associated histone mark H3K27ac to identify a candidate Aire cis-regulatory element. There is enrichment of H3K27ac near this element, ACNS1, in mTECs and the element also has characteristics of being NF-κB-responsive. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance.
2015-10-23 | GSE74257 | GEO
Project description:We describe, MARGE, Model-based Analysis of the Regulation of Gene Expression, a robust methodology that leverages a large library of genome-wide H3K27ac ChIP-seq profiles to predict key regulated genes and cis-regulatory regions in human or mouse. MARGE adopts a gene centric approach to define a regulatory potential that summarizes the aggregate activity of multiple cis-regulatory elements on each gene. This model is effective in describing cis-regulatory activity and, unlike the super-enhancer based approach, is highly predictive of gene expression changes in response to BET-bromodomain inhibitors. We show that linear combinations of H3K27ac defined regulatory potentials, selected from an extensive database of published H3K27ac profiles, can accurately model diverse gene sets derived from differential gene expression experiments. In addition, we demonstrate a novel semi-supervised learning approach for identifying transcription factor binding sites associated with the set of transcription factors that regulate the gene set. MARGE leverages published H3K27ac ChIP-seq data to enhance the interpretation of newly generated H3K27ac ChIP-seq profiles. MARGE can also be used to analyze gene expression studies, without the production of matched H3K27ac ChIP-seq data. Identifying genomic profiles of histone modification H3K27ac in LNCaP-abl cell line after siRNA knock down of a series of gene factors.
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Project description:We describe, MARGE, Model-based Analysis of the Regulation of Gene Expression, a robust methodology that leverages a large library of genome-wide H3K27ac ChIP-seq profiles to predict key regulated genes and cis-regulatory regions in human or mouse. MARGE adopts a gene centric approach to define a regulatory potential that summarizes the aggregate activity of multiple cis-regulatory elements on each gene. This model is effective in describing cis-regulatory activity and, unlike the super-enhancer based approach, is highly predictive of gene expression changes in response to BET-bromodomain inhibitors. We show that linear combinations of H3K27ac defined regulatory potentials, selected from an extensive database of published H3K27ac profiles, can accurately model diverse gene sets derived from differential gene expression experiments. In addition, we demonstrate a novel semi-supervised learning approach for identifying transcription factor binding sites associated with the set of transcription factors that regulate the gene set. MARGE leverages published H3K27ac ChIP-seq data to enhance the interpretation of newly generated H3K27ac ChIP-seq profiles. MARGE can also be used to analyze gene expression studies, without the production of matched H3K27ac ChIP-seq data.
2016-05-16 | GSE72534 | GEO
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