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| Status |
Public on Sep 25, 2024 |
| Title |
SATB1 prevents immune cell infiltration by regulating chromatin organization and gene expression of a chemokine gene cluster in T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The precise regulation of T lymphocyte development and functions is crucial for preventing the initiation and progression of autoimmunity. SATB1, a key regulator of T cell development, governs lineage-specific transcriptional programs. However, its role in autoimmunity remains unclear. Here we show that conditional knockout of Satb1 in CD4+ T cells in mice led to T cell hyperactivation and inflammatory cell infiltration in the lungs and stomach. By performing transcriptome profiling, we show that the loss of SATB1 led to the aberrant upregulation of chemokines, particularly the ones belonging to the CC subfamily. Treating Satb1 conditional knockout mice with the inhibitor of the CC chemokine receptor alleviated inflammatory cell infiltration and autoimmune phenotypes. Intriguingly, SATB1's transcriptional regulation of chemokine genes could not be attributed to its direct binding to chemokine promoters or modulation of H3K27Ac. Instead, SATB1 exerted its regulatory effects through the control of higher-order chromatin organization at the CC chemokine locus. The loss of SATB1 led to the emergence of a new chromatin domain encompassing the Ccl3, Ccl4, Ccl5, Ccl6, and Ccl9 genes and a distal enhancer, resulting in increased contacts between the enhancer and all five chemokine genes, thus inducing their upregulation. Collectively, these results demonstrate that SATB1 safeguards organisms against autoimmunity by ensuring proper chemokine expression and preventing inflammatory cell infiltration, providing valuable insights into the understanding of autoimmune diseases.
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| Overall design |
Refer to individual Series
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| Citation(s) |
39394451 |
| |
| Submission date |
Feb 09, 2023 |
| Last update date |
Nov 22, 2024 |
| Contact name |
bao wang |
| Organization name |
shanghai jiao tong university school of medicine
|
| Street address |
jin zun road
|
| City |
shanghai |
| ZIP/Postal code |
200000 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (10)
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| This SuperSeries is composed of the following SubSeries: |
| GSE224975 |
SATB1 prevents immune cell infiltration by regulating chromatin organization and gene expression of a chemokine gene cluster in T cells [CUT&Tag] |
| GSE224976 |
SATB1 prevents immune cell infiltration by regulating chromatin organization and gene expression of a chemokine gene cluster in T cells [RNA-seq] |
|
| Relations |
| BioProject |
PRJNA933204 |
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