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Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells

ABSTRACT: Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells

PROVIDER: PRJNA472356 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7190750_1.fastq.gz	Fastqsanger.gz
	SRR7190750_2.fastq.gz	Fastqsanger.gz
	SRR7190760_1.fastq.gz	Fastqsanger.gz
	SRR7190760_2.fastq.gz	Fastqsanger.gz
	SRR7190770_1.fastq.gz	Fastqsanger.gz

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Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells

Project description:Thymic epithelial cells (TEC) effect crucial roles in thymopoiesis including the control of negative thymocyte selection. This process depends on their capacity to express promiscuously genes encoding tissue-restricted antigens. This competence is accomplished in medullary TEC (mTEC) in part by the presence of the transcriptional facilitator AutoImmune REgulator, AIRE. AIRE-regulated gene transcription is marked by repressive chromatin modifications, including H3K27me3. When during TEC development these chromatin marks are established, however, remains unclear. Here we use a comprehensive ChIP-seq dataset of multiple chromatin modifications in different TEC subtypes to demonstrate that the chromatin landscape is established early in TEC differentiation. Much of the chromatin architecture found in mature mTEC was found to be present already over earlier stages of mTEC lineage differentiation. This was reflected by the fact that a machine learning approach accurately classified genes as AIRE-induced or AIRE-independent both in immature and mature mTEC. Moreover, analysis of TEC specific enhancer elements identified candidate transcription factors likely to be important in mTEC development and function. Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC.

2018-08-28 | GSE114713 | GEO

Comprehensively Profiling the Chromatin Architecture of Tissue Restricted Antigen Expression in Thymic Epithelial Cells Over Development.

Project description:Thymic epithelial cells (TEC) effect crucial roles in thymopoiesis including the control of negative thymocyte selection. This process depends on their capacity to express promiscuously genes encoding tissue-restricted antigens. This competence is accomplished in medullary TEC (mTEC) in part by the presence of the transcriptional facilitator AutoImmune REgulator, AIRE. AIRE-regulated gene transcription is marked by repressive chromatin modifications, including H3K27me3. When during TEC development these chromatin marks are established, however, remains unclear. Here we use a comprehensive ChIP-seq dataset of multiple chromatin modifications in different TEC subtypes to demonstrate that the chromatin landscape is established early in TEC differentiation. Much of the chromatin architecture found in mature mTEC was found to be present already over earlier stages of mTEC lineage differentiation as well as in non-TEC tissues. This was reflected by the fact that a machine learning approach accurately classified genes as AIRE-induced or AIRE-independent both in immature and mature mTEC. Moreover, analysis of TEC specific enhancer elements identified candidate transcription factors likely to be important in mTEC development and function. Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC.

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Tissue restricted antigen expression by medullary thymic epithelial cell subsets induces distinct autoreactive T cell fates

Project description:Tissue restricted antigen expression by medullary thymic epithelial cell subsets induces distinct autoreactive T cell fates

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Tissue restricted antigen expression by medullary thymic epithelial cell subsets induces distinct autoreactive T cell fates

Project description:Cellular interactions in the thymus play an essential role in ensuring the development of a self-tolerant T cell repertoire. Medullary thymic epithelial cells (mTECs) contribute to tolerance by expressing and presenting tissue-restricted antigens (TRA) so that developing T cells can assess the self-reactivity of their antigen receptors prior to leaving the thymus. This has largely been studied in the context of autoimmune regulator (Aire) dependent TRA expression in mature mTECs. Yet, mTECs are a heterogeneous population of cells that differentially express unique pools of TRA, and whether mTEC subsets induce distinct autoreactive T cell fates remains unclear. Here we attribute unique roles for mTEC subsets in directing distinct mechanisms of T cell tolerance that significantly impact infection and tumor control. These results have important implications in the design of effective therapeutic approaches that aim to modulate the function of self-reactive T cells.

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Project description:Antigen presentation by cortical and medullary thymic epithelial cells (cTEC and mTEC) ensures the formation of a self-restricted and self-tolerant T cell repertoire, respectively. As such, a broad diversity of self-antigens needs to be presented by mTEC to induce T cell’s self-tolerance. Even though the expression and antigen presentation of protein coding genes in mTEC has been abundantly described, little is known of the implication of allegedly noncoding regions of the genome to tolerance induction. In this study, we focused on transposable elements (TE), which have been shown to be highly expressed by mTEC.

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Mapping the thymic hematopoietic antigen presenting cell network

Project description:Mapping the thymic hematopoietic antigen presenting cell network

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Chromatin immunoprecipitation and ATAC-Seq data from meduallar thymic epithelial cells [ChIP-Seq]

Project description:Aire is a transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We used Affymetrix microarrays to analyze the gene expression patterns of Aire expressing cells (mature mTECs and Thymic B cells) and compared them to control counterparts, namely immature mTECs, cortical Thymic epithelial cells and splenic B cells of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We’ve used Assay for transposase-accessible chromatin using sequencing (ATAC-Seq) on the different thymic epithelial cell populations to assess chromatin accessibility around the Aire locus in these cells. Moreover, we’ve used the indexing-first chromatin immunoprecipitation (iChIP) technique to assess the occupancy of the Irf8 transcription factor in the Aire locus

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Chromatin immunoprecipitation and ATAC-Seq data from meduallar thymic epithelial cells [ATAC-Seq]

Project description:Aire is a transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We used Affymetrix microarrays to analyze the gene expression patterns of Aire expressing cells (mature mTECs and Thymic B cells) and compared them to control counterparts, namely immature mTECs, cortical Thymic epithelial cells and splenic B cells of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We’ve used Assay for transposase-accessible chromatin using sequencing (ATAC-Seq) on the different thymic epithelial cell populations to assess chromatin accessibility around the Aire locus in these cells. Moreover, we’ve used the indexing-first chromatin immunoprecipitation (iChIP) technique to assess the occupancy of the Irf8 transcription factor in the Aire locus

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