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Satb1 Overexpression Drives Tumor-Promoting Activities In Cancer-Associated Dendritic Cells

ABSTRACT: Special AT-rich sequence-binding protein-1 (Satb1) governs genome-wide transcriptional programs. Using a new conditional knockout mouse, we found that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating MHC-II expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC-II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46+ inflammatory DCs that universally infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. Correspondingly, specific in vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but relentless Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression. RNA-seq with whild type and knocked-down Satb1

ORGANISM(S): Mus musculus

SUBMITTER: Priyankara Wickramasinghe

PROVIDER: E-GEOD-76776 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Satb1 Overexpression Drives Tumor-Promoting Activities In Cancer-Associated Dendritic Cells

Project description:Special AT-rich sequence-binding protein-1 (Satb1) governs genome-wide transcriptional programs. Using a new conditional knockout mouse, we found that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating MHC-II expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC-II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46+ inflammatory DCs that universally infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. Correspondingly, specific in vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but relentless Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.

2016-01-13 | GSE76776 | GEO

Expression data of control-shRNA and SATB1-shRNA expressing MDA-MB-231 cells from 2D and 3D culture system

Project description:We examined whether SATB1 functions as a global gene regulator in order to maintain the aggressive phenotype of the MDA-MB-231 cell line. We compared the gene expression profiles between control_shRNA-MDA-MB-231 cells, which express SATB1 at high levels, and SATB1_shRNA1-MDA-MB-231 in which the level of SATB1 was greatly downregulated by RNAi technology. This comparative studies were performed using two different platforms (Codelink and Affymetrix genechip) with two culture conditions either on plastic dish (2D) or on matrigel (3D) which allows cells to form a breast-like morphology only for non-aggressive cells. Keywords: Comparative studies on Control_shRNA and SATB1_shRNA1 expressing MDA-MB-231 from 2D or 3D culture. We examined control_shRNA-MDA-MB-231 cells and SATB1_shRNA1-MDA-MB-231 cells under two culture condition;on plastic dish(2D culture) and on Matrigel coated dish(3D culture). When SATB1 was depleted by RNAi technology, these normally aggressive cells exhibited normal breast like morphology on 3D. We used two different microarray platforms (Codelink and Affymetrix) to make expression data. Initial analysis of data and cross-platform comparison were performed using Codelink expression analysis and GeneSpring software. We provide ratio for control_shRNA/SATB1_shRNA1-MDA-MB-231 cells for 2D and 3D on this series.

2010-05-26 | E-GEOD-5417 | biostudies-arrayexpress

RNA-SEQ of Satb1-knockdown in dopaminergic neurons from the mouse mid-brain

Project description:RNA-SEQ profiling of mouse dopaminergic neurons from the mouse mid-brain, with AAV1 injections using a Satb1 shRNA-EGFP construct or a scrambed shRNA-EGFP construct Murine midbrain dopaminergic neurons with Satb1 shRNA treatment or scrambled control

2015-07-27 | E-GEOD-70133 | biostudies-arrayexpress

Transcriptome of SATB1 transduced Hut78 cells

Project description:Hut78 cell line was used as Sezary syndrome cell model. Comparative transcriptome profiles of SATB1 transduced Hut78 cells (Hut78-SATB1) relative to empty MIG vector transduced control Hut78 cells (Hut78-MIG) were analyzed. The primary goal is to establish a list of genes with differential expression between SATB1 transduced Hut78 cells and control Hut78 cells to identify the gene expression regulation effect of SATB1 expression in Sezary cells. Two color experiment, 3 biological replicates (3 unique cell clones) with Hut78 cells, each compared with a distinct individual clone from cells transduced with empty MIG vector.

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ChIP-seq of SATB1-bound regions in human ESC-derived dopaminergic (DA) neurons at different time points. ATAC-Seq and RNA-Seq of DA and cortical neurons (WT and SATB1-KO)

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2019-09-20 | E-MTAB-5965 | biostudies-arrayexpress

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

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Genome-wide maps of DNA cytosine methylation state in during normal differentiation commitment in hematopoietic stem cells (HSC) and in Special AT-rich sequence-binding protein1 (Satb1) - deficient HSC

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Reshaping of the MHC-I ligandome in response to reovirus-based cancer immunotherapy

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2019-05-20 | PXD013066 | Pride

SATB1 prevents immune cell infiltration by regulating chromatin organization and gene expression of a chemokine gene cluster in T cells [RNA-seq]

Project description: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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SATB1 prevents immune cell infiltration by regulating chromatin organization and gene expression of a chemokine gene cluster in T cells

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