Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ChIP-seq analysis of H3K9me3 signal from T-ALL cell line (Jurkat) upon fast CXCL12 stimulation

ABSTRACT: T-acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy, which comprises the accumulation of malignant T-cell precursors. Despite current therapies, up to 20% of children with failure to respond to treatments and relapse. Our understanding of T-ALL infiltration and how leukaemia cells-microenvironment interactions play a role in the clinical outcome is still vague. In the present study, we showed a novel function of the chemokine CXCL12, which induced fast epigenetic changes within minutes in cell lines and primary T-ALL cells. Our results identified that CXCL12-mediated H3K9 methylation impacted on the global chromatin configuration and the nuclear mechanics of T-ALL cells. We characterised changes in the transcriptional profile of T-ALL cells associated with rapid CXCL12 stimulation. We demonstrated that cytoskeletal changes and protein kinase-C (PKC) activity were the molecular mechanisms by which CXCL12 promoted H3K9 methylation in T-ALL cells. Furthermore, targeting H3K9 methyltransferases reduced the migration and the nuclear deformability in both cell line and primary human ALL cells. Together, our data indicate a novel funcion of H3K9 methylation induced by CXCL12 in T-ALL cells, that reveals the significance of nuclear changes to mechanobiology and function of leukemia cells and emerges as a promising pharmacological target against T-ALL infiltration and dissemination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162605 | GEO | 2021/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data changes induced by CXCL12 in T-ALL cells

Project description:Our results identified that CXCL12-mediated H3K9 methylation impacted on the global chromatin in the transcriptional profile of T-ALL cells.

2021-01-31 | GSE162134 | GEO

Complete loss of H3K9 methylation dissolves mouse heterochromatin organization

Project description:Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all 6 SET domain methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEFs no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is the first analysis of H3K9 methylation deficient mammalian chromatin and reveals a crucial function for H3K9 methylation in protecting heterochromatin organization and genome integrity.

2021-05-27 | PXD018175 | Pride

T cell-mediated development of stromal fibroblasts with an immune-enhancing chemokine profile [single-cell RNA-seq]

Project description:Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how fibroblasts adapt to these contrasting microenvironments remains unknown. Cancer-associated fibroblasts (CAFs) mediate immune quiescence by producing the chemokine CXCL12, which coats cancer cells to suppress T cell infiltration. We examined whether CAFs can also adopt an immune-promoting chemokine profile. Single-cell RNA-sequencing of CAFs from mouse pancreatic adenocarcinomas identified a sub-population of CAFs with decreased expression of CXCL12 and increased expression of the T cell-attracting chemokine, CXCL9 in association with T cell infiltration. TNFa and IFNg containing conditioned media from activated CD8+ T cells converted stromal fibroblasts from a CXCL12+/CXCL9- immune suppressive phenotype into a CXCL12-/CXCL9+ immune-activating phenotype. Recombinant IFNg and TNFa acted synergistically to induce CXCL9 expression, whereas TNFa alone suppressed CXCL12 expression. This coordinated chemokine switch leads to increased T cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.

2023-04-03 | GSE228836 | GEO

T cell-mediated development of stromal fibroblasts with an immune-enhancing chemokine profile [bulk RNA-seq]

2023-04-03 | GSE228835 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of EL4+Ctrl and EL4+RGFP966 cells' Transcriptomes in T cells lymphoma

Project description:We here reported that HDAC3 inhibition induces the infiltration of NK cells in lymphoma and enhances their cytotoxicity by promoting the secretion of CXCL12 from lymphoma cells. RNA-seq analysis of EL4 cells treated with or without RGFP966 showed that chemokine signaling was significantly enriched in the HDAC3 inhibitor-treated group. And the expression of CXCL12 in mRNA and protein level were increased. ATF3 overexpression decreased the mRNA level of CXCL12 in lymphoma cells and reduced CXCL12 transcription can be reversed by HDAC3 inhibition in H9 cells. To sum up, targeting HDAC3 promoted the secretion of CXCL12 by inhibiting ATF3’s transcriptional activity.

2024-04-18 | GSE243346 | GEO

Global chromatin relabeling accompanies spatial inversion of chromatin in rod photoreceptors

Project description:We used CUT&RUN sequencing technology for high-throughput profiling of histone modifications in murine rod photoreceptor cells during post-natal maturation. We generated genome-wide chromatin-state maps of mouse embryonic stem cells, and rod cells isolated from post-natal days 1, 7, 14, 21, and adult mice. We find that Histone H3 Lysine 9 methylation status changes over the course of rod cell maturation, accompanying the transition of nuclear architecture from "conventional" to "inverted" such that H3K9me2-labeled nuclear peripheral heterochromatin is relabeled with H3K9me3 and repositioned to the nuclear center, while transcriptionally active euchromatin is labeled with H3K9me2 and positioned at the nuclear periphery. Global chromatin relabeling is correlated with spatial rearrangement, suggesting a critical role for histone modifications, specifically H3K9 methylation, in nuclear architecture.

2021-09-29 | GSE180006 | GEO

Tumor microenvironment and transcriptional analysis of CD45+ leukocytes isolated from syngeneic MC38 tumors from mice fed ketogenic diet or control diet

Project description:Tumor microenvironment (TME) has a dynamic composition that affects targeted therapies for colorectal cancer (CRC). Cancer associated fibroblasts (CAFs) direct and induce infiltration of immunosuppressive cells through secreted cytokines such as CXCL12. Here, we show that decreased ketogenesis is a signature of CRCs and that an increase in ketogenesis, using a ketogenic diet (KD), decreases CXCL12 in CAFs, tumors, serum, livers, and lungs. Increase in ketogenesis results in the decreased expression of KLF5, which binds to the CXCL12 promoter and induces CXCL12 expression. KD decreases intratumoral accumulation of M2 macrophages and myeloid-derived suppressor cells (MDSCs), increases infiltration of NK and cytotoxic T cells and enhances the anticancer effects of PD-1 blockade in murine-derived CRCs. Moreover, an increase in ketogenesis inhibits CRC migration, invasion, and metastasis in vitro and in vivo. Importantly, our studies demonstrate that downregulation of de novo ketogenesis in the TME is a critical step in CRC progression.

2022-04-27 | GSE180110 | GEO

KMT1E Mediated H3K9 Methylation Is Required for the Maintenance of Embryonic Stem Cells by Repressing Trophectoderm Differentiation

Project description:Dynamic regulation of histone methylation by methyltransferases and demethylases plays a central role in regulating the fate of embryonic stem (ES) cells. The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene results in peri-implantation lethality and prevents the propagation of ES cells. However, Setdb1- null blastocysts do not display global changes in H3K9 methylation or DNA methylation, arguing against a genome- wide defect. Here we show that conditional deletion of the Setdb1 gene in ES cells results in the upregulation of lineage differentiation markers, especially trophectoderm-specific factors, similar to effects observed upon loss of Oct3/4 expression in ES cells. We demonstrate that KMT1E deficiency in ES cells leads to a decrease in histone H3K9 methylation at and derepression of trophoblast-associated genes such as Cdx2. Furthermore, we find genes that are derepressed upon Setdb1 deletion to overlap with known targets of polycomb mediated repression, suggesting that KMT1E mediated H3K9 methylation acts in concert with polycomb controlled H3K27 methylation. Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells. Analysis of KMT1E-deficiency in mouse embryonic stem cells using a Setdb1 conditional allele and tamoxifen-inducible Cre/loxP recombination

2011-04-15 | E-GEOD-28593 | biostudies-arrayexpress

Spatial organization of H3K9me2/3-marked heterochromatin is redundantly maintained by either the H3K9 or H3K27 methylation pathway [Hi-C]

Project description:Heterochromatin is a key architectural feature of eukaryotic chromosomes, which is critical for cell type specific gene expression and genome stability. In the mammalian nucleus, heterochromatin is segregated from transcriptionally active genomic regions, and exists as large condensed and inactive nuclear compartment. However, the underlying mechanism of spatial organization of heterochromatin is still poorly understood. Histone H3 lysine 9 di- and tri-methylation (H3K9me2/3) and lysine 27 trimethylation (H3K27me3) are two major epigenetic modifications that define constitutive and facultative heterochromatin, respectively. In mammals, there are at least five H3K9 methyltransferases (SUV39H1, SUV39H2, SETDB1, G9a and GLP) and two H3K27 methyltransferases (EZH1 and EZH2). In this study, we addressed the role of H3K9 and H3K27 methylation in heterochromatin organization by using a combination of compound mutant cells for the five H3K9 methyltransferases and an EZH1/2 dual inhibitor, DS3201. We show that H3K27me3, which is normally segregated from H3K9me2/3, was redistributed to regions targeted by H3K9me2/3 after the loss of H3K9 methylation, and loss of both H3K9 and H3K27 methylation resulted in impaired both condensation and spatial organization of heterochromatin. Our data demonstrate that the two major repressive epigenome pathways exclusively but also coordinately maintain H3K9me2/3-marked heterochromatin organization in mammalian cells.

2022-04-05 | GSE200012 | GEO

Spatial organization of H3K9me2/3-marked heterochromatin is redundantly maintained by either the H3K9 or H3K27 methylation pathway [RNA-Seq]

2022-04-05 | GSE200015 | GEO