Role of interleukin 2 on SATB1 binding in SP CD4+ thymocytes
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ABSTRACT:
PROVIDER: PRJNA480014 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7478870_1.fastq.gz | Fastqsanger.gz | |||
| SRR7478870_2.fastq.gz | Fastqsanger.gz | |||
| SRR7478871_1.fastq.gz | Fastqsanger.gz | |||
| SRR7478871_2.fastq.gz | Fastqsanger.gz | |||
| SRR7478866_1.fastq.gz | Fastqsanger.gz |
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Project description:CD4+ and CD8+ double-positive (DP) thymocytes are at a critical stage during the T cell development in thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCR. Then DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, Regulatory T cells, or invariant nature kill T cells (iNKT) according to the TCR signal. Chromatin organizer SATB1 is highly expressed in DP cells and plays an essential role in regulating Tcra rearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing assay of SATB1-deficient thymocytes showed that the cell identity of DP thymocytes was changed, and the genes specifically highly expressed in DP cells were down-regulated. ChIP-seq and ATAC-seq data showed the similar tendency. The super-enhancers regulate the expressions of the DP-specific genes, and the SATB1 deficiency reduced the super-enhancer activity. Hi-C data showed that interactions in super-enhancers and between super-enhancers and promoters decreased in SATB1 deficient thymocytes. We further explored the regulation mechanism of two SATB1-regulating genes, ETS2 and Bcl6, in DP cells and found that the knockout of the super-enhancers of these two genes impaired the development of DP cells. Our research reveals that SATB1 globally regulates super-enhancers of DP cells and promotes the establishment of DP cell identity, which helps understand the role of SATB1 in thymocyte development.
2021-09-02 | GSE182995 | GEO
Project description:T-cell receptor (TCR) signaling by MHC class-I and -II induces thymocytes to acquire cytotoxic and helper fates via induction of Runx3 or ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. We show that a genome organizer, Satb1, activates genes for lineage-specifying factors, including ThPOK and Runx3, in post-selection thymocytes. Indeed, Satb1-deficient thymocytes are partially redirected to inappropriate T lineages after MHC selection. Although Satb1 is dispensable for maintaining ThPOK in CD4+ T cells, it is necessary for restraining expression of the Treg factor FoxP3. Collectively, our findings demonstrate that Satb1 shapes the primary T-cell pool by initially directing lineage-specific transcriptional programs and subsequently balancing effector versus regulatory subsets via FoxP3 repression.
2017-01-19 | GSE77000 | GEO
Project description:T-cell receptor (TCR) signaling by MHC class-I and -II induces thymocytes to acquire cytotoxic and helper fates via induction of Runx3 or and ThPOK transcription factors, respectively. The mechanisms by The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. It remains elusivewhich how TCR signaling is translated into transcriptional programs for each cell fate remain elusive. We show that a genome organizer, SATB1, activates genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8 and Treg factor Foxp3, and Treg factor Foxp3, and CD4, and /CD8, in post-selection thymocytes. Indeed, SATBatb1-deficient thymocytes are partially redirected into inappropriate T lineages after both MHC class-I and -II mediated selection, and fail to generate Treg subset. Despite its essential role in initiating regulatory regions activity in TCR signaled thymocytes. SATBatb1 is becomes dispensable for maintaining ThPOK in CD4+ T cells. Collectively, our findings demonstrate that SATBatb1 shapes the primary T-cell pool by initially directing lineage-specific transcriptional programs in the thymus.
2017-05-23 | GSE90635 | GEO
Project description:Interleukine 2 (IL-2) is still one of the most interesting cytokines in T cell biology with its ability to control immune homeostasis by maintaining the functional identity of Foxp3+ regulatory T (Treg) cells and the expansion of activated conventional T (Tconv) cells. Yet, how IL-2 exactly enables Treg cells to suppress autoreactive Tconv cells and to maintain their identity is unclear. Using a mouse model in which IL-2 signaling via its high affinity receptor CD25 is selectively impaired, the “Il2ramut/mut” mouse, we report that Treg cells that only receive low IL-2 signals keep Il2ramut/mut but not WT Tconv cells “in check”, suggesting equal IL-2 signals in Treg and Tconv cells is essential to safeguard immune homeostasis. Furthermore, the comparative analysis of gene expression and epigenetic landscape of Il2ramut/mut and WT Treg cells support a model in which IL-2 "locks in” Treg cell identity and functions in vivo by controlling their genome-wide chromatin accessibility.
2018-11-21 | GSE116736 | GEO
Project description:Role of interleukin 2 on Foxp3+CD4+ regulatory T (Treg) cell gene expression and chromatin modeling in thymus and lymph node, and on SATB1 DNA binding in single positive CD4 thymocytes
| PRJNA400557 | ENA
Project description:The generation of mature CD4⁺ helper and CD8⁺ cytotoxic T cells from double-positive (DP) thymocytes is a central step in building an effective adaptive immune system. This process relies on positive selection, whereby αβTCR⁺ thymocytes are tested for recognition of self-peptide–MHC complexes presented by cortical thymic epithelial cells. Thymocytes with insufficient signaling die by neglect, while those receiving appropriately tuned signals survive and differentiate. Positive selection thus plays a dual role: establishing MHC restriction and directing lineage commitment into the CD4 or CD8 fate. After TCR rearrangement is completed, T cells can interact with APCs to transmit TCR signals and produce CD69 protein. SO, CD69+DP cells is undergoing positive selection. Here, we explored the mechanism of SATB1 regulating thymocyte positive selection. Firstly, We analysis the function of SATB1 in the transtion of CD69-DP to CD69+DP by CUT&Tag, ATAC and HiC assays. Then, Single-cell RNA sequencing assay of SATB1-deficient thymocytes showed that the cell identity of CD69+DP thymocytes was changed, and the genes differently expressed in CD69+DP cells. Smart-seq2 showed the similar tendency. CUT&Tag , ATAC-seq and HiC data show the mechanism for SATB1 in T cell positive selection or before this stage. ACC-seq confirms that SATB1 forms phase separation at these sites and regulates gene expression, These data helps us to understand the role of SATB1 in thymocyte positive selection.
2025-12-19 | GSE313769 | GEO
Project description:Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor induced by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. In this study, we investigated the role of SATB1 in T helper cell differentiation by performing ChIP-on-chip analysis of human cord blood CD4+ T cells cultured in Th1 and Th2 conditions. These results were combined with gene expression profiling results from human differentiating Th cells in which expression of SATB1 was downregulated by RNA interference (RNAi).Our results indicate that SATB1 regulates and is bound to sixty genes in primary human CD4+ T cells, including several IL-12 and/or IL-4 regulated factors, suggesting a role in the development or function of Th subtypes. Cross-linked chromatin obtained from human CD4+ T cells isolated from cord blood cultured in Th1 and Th2 conditions for 24 h was immunoprecipitated with anti-SATB1 antibody.
2010-05-16 | E-GEOD-17380 | biostudies-arrayexpress
Project description:Rag1 and Rag2 gene expression in CD4+CD8+ double positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. Sequencing of Satb1-ChIP and input control from 6 wk old thymus
2015-02-25 | E-GEOD-66248 | biostudies-arrayexpress
Project description:Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by compacting super-enhancers
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Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases.
2025-05-20 | GSE250577 | GEO