Transcription factor Satb1 modulates the functionality of peripheral Treg cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE190914 | GEO | 2024/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:Transcription factor Satb1 plays important roles in the development of various immune cells. By utilizing genetic tools such as conditional knockout in mice have provided valuable information about its roles in T cell development. For example, CD4-cre transgenic mouse has been extensively used to delete Satb1 gene from T cells. While CD4-cre is useful to knockout a target gene floxed by LoxP sites from T cells, its expression lacks tissue specificity. To decipher the specific roles of Satb1 in T cells, we generated Satb1 conditional knockout mice with ThPOK-cre and E8I-cre to delete Satb1 from peripheral CD4+ and CD8+ T cells, respectively. Subsequently, total RNA-seq was performed to examine changes in transcriptome in the absence of Satb1 from peripheral T cells.
2024-08-01 | GSE190948 | GEO
Project description:Transcription factor Satb1 plays important roles in the development of various immune cells. By utilizing genetic tools such as conditional knockout in mice have provided valuable information about its roles in T cell development. For example, CD4-cre transgenic mouse has been extensively used to delete Satb1 gene from T cells. While CD4-cre is useful to knockout a target gene floxed by LoxP sites from T cells, its expression lacks tissue specificity. To decipher the specific roles of Satb1 in T cells, we generated Satb1 conditional knockout mice with ThPOK-cre and E8I-cre to delete Satb1 from peripheral CD4+ and CD8+ T cells, respectively. Subsequently, total RNA-seq was performed to examine changes in transcriptome in the absence of Satb1 from peripheral T cells.
2024-08-01 | GSE190629 | GEO
Project description:This data represent characterization of the interactome of murine Thpok. A version of Thpok (Thpok-Bio) subject to biotinylation in vivo by the BirA biotin ligase was used; to assess Thpok interactions in primary cells, Thpok-Bio was retrovirally expressed in in vitro activated CD4+ T cells from Thpokfl/fl Ox40-Cre+ mice carrying a Rosa26BirA allele. Expression of Ox40-Cre, initiated upon T cell activation, causes the deletion of endogenous Thpokfl alleles, so that transduced cells only express Thpok-Bio. Two Thpok deletion constructs (BKK and RFK) were also analyzed. Following streptavidin pulldown, proteins were separated by SDS-PAGE, the full lane cut into 9 slices, and in-gel digested. FIles are: 1384 - empty vector; 1385 - Thpok; 1386 - Thpok + Ethidium Bromide; 1387 - Thpok BKK; 1388 - Thpok RFK.
| MSV000088126 | MassIVE
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:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of RNA-Seq experiments is a part of SuperSeries including also ATAC-Seq, Hi-C and HiChIP experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. RNA-Seq experiments supported the repressive nature of Satb1 cKO nuclear environment and together with the other datasets it showed that SATB1 functions primarily as an activator. SATB1 mediates promoter-enhancer chromatin loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional and ubiquitously expressed genome organizers.
2022-09-23 | GSE173470 | GEO
Project description:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of ATAC-Seq experiments is a part of SuperSeries including also RNA-Seq, Hi-C and HiChIP experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. ATAC-Seq experiments supported the repressive nature of Satb1 cKO nuclear environment and together with the other datasets it showed that SATB1 functions primarily as an activator. SATB1 mediates promoter-enhancer chromatin loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional and ubiquitously expressed genome organizers.
2022-09-23 | GSE173445 | GEO
Project description:Autoimmune diseases are systemic diseases caused by abnormalities of the immune system. Satb1 is a nuclear protein highly expressed in T cells and plays an important role in regulating the expression of T cell functional genes. However, its role in autoimmune diseases remains unclear. Our study found that conditional knockout of Satb1 in CD4+ T cells led to T cell hyperactivation and inflammatory cell infiltration in the lungs and stomach. By performing transcriptome profiling, we showed that the loss of SATB1 led to the aberrant upregulation of chemokines, particularly the ones belonging to the CC subfamily. We further found that SATB1 could bind to the promoters of CC chemokines and reduce the levels of H3K27ac, thereby repressing the expression of these genes. Such a transcriptional repressive function is likely attributed to the ability of SATB1 to recruit HDAC1. Treating Satb1 conditional knockout mice with the inhibitor of the CC chemokine receptor alleviated inflammatory cell infiltration and autoimmune phenotypes. Collectively, these results demonstrate that Satb1 plays a critical role in regulating chemokine expression and preventing inflammatory cell infiltration, providing new perspectives on the understanding and clinical treatment of autoimmune diseases.
2024-09-27 | GSE224975 | GEO
Project description:The transcription factor Thpok is essential for CD4 T cell development in the thymus and remains expressed in post-thymic CD4 T cells. We post-thymically inactivated Thpok and compared microarray gene expression in Thpok-deficient CD4 T cells to that in their wildtype CD4 or CD8 counterparts We show that Thpok constrains the transcriptional circuitry to maintain CD4+-lineage integrity in naM-CM-/ve cells and to couple effector differentiation to environmental cues after antigenic stimulation. Redundantly with the related factor LRF, Thpok is continuously needed to prevent the trans-differentiation of mature CD4+ into -CD8+ T cells. We activated naM-CM-/ve CD4 T cells (either wild-type or Thpok-deficient) and CD8 T cells (wild-type) in vitro under Th1 conditions. Differentiated effectors were sorted 4 days after activation into CD4+CD8- and CD4-CD8+ (wild-type) and CD4+CD8- and CD4+CD8+ (Thpok-deficient) subsets. Total RNA was extracted from sorted subsets and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturerM-bM-^@M-^Ys recommendation. Data is from 3 replicates (except wild-type CD4-CD8+ cells, for which two samples only were processed), generated from two distinct cell preparations.
2014-08-15 | E-GEOD-57846 | biostudies-arrayexpress
Project description:Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of Hi-C and HiChIP experiments is a part of SuperSeries including also RNA-Seq and ATAC-Seq experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. Utilizing the HiChIP data, we compared SATB1 and CTCF-mediated chromatin loops, revealing that SATB1 builds a more refined layer of genome organization upon the CTCF scaffold. Moreover, H3K27ac HiChIP and Hi-C experiments in WT and Satb1 cKO thymocytes helped us to assess the functional impact of SATB1 and its underlying genome-wide regulome. SATB1 primarily mediates promoter-enhancer loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional ubiquitously expressed genome organizers.
2022-09-23 | GSE173446 | GEO
Project description:We show here that the T helper-fate is not fixed and that mature antigen-stimulated CD4 T cells can switch off Thpok expression and reactivate CD8- lineage genes. This unexpected plasticity results in the post-thymic termination of the T helper- program and the functional differentiation of distinct MHC class II restricted CD4 cytotoxic T lymphocytes Small intestine CD4 intraepithelial T lymphocytes from ThPOK-GFP reposter mice were isolated and sorted (FACS Aria) based on ThPOK and CD8aa expression. Cell were isolated either from non-experimental ThPOK-GFP reporter mice (WT) or after transfering CD4 naive T cells from ThPOK-GFP reporter mice to RAG-/-recipient animals (TR) as an experimental colitis model. Experimet was done in duplicate.
2012-12-10 | E-GEOD-42277 | biostudies-arrayexpress