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Methyltransferase Inhibitors Restore SATB1 Protective Activity Against Cutaneous T cell Lymphoma

ABSTRACT: Methyltransferase Inhibitors Restore SATB1 Protective Activity Against Cutaneous T cell Lymphoma

PROVIDER: PRJNA670965 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12884761_1.fastq.gz	Fastqsanger.gz
	SRR12884761_2.fastq.gz	Fastqsanger.gz
	SRR12884762_1.fastq.gz	Fastqsanger.gz
	SRR12884762_2.fastq.gz	Fastqsanger.gz
	SRR12884763_1.fastq.gz	Fastqsanger.gz

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Methyltransferase inhibitors restore SATB1 protective activity against cutaneous T cell lymphoma in mice.

Project description:Cutaneous T cell lymphoma (CTCL) has a poorly understood etiology and no known cure. Using conditional knockout mice, we found that ablation of the genomic organizer special AT-rich sequence-binding protein 1 (Satb1) caused malignant transformation of mature, skin-homing, Notch-activated CD4+ and CD8+ T cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation and the expression of skin-homing chemokine receptors in mature T cells. Notably, methyltransferase-dependent epigenetic repression of SATB1 was universally found in human Sézary syndrome, but not in other peripheral T cell malignancies. H3K27 and H3K9 trimethylation occluded the SATB1 promoter in Sézary cells, while inhibition of SUV39H1/2 methyltransferases (unlike EZH2 inhibition) restored protective SATB1 expression and selectively abrogated the growth of primary Sézary cells more effectively than romidepsin. Therefore, inhibition of methyltransferases that silence SATB1 could address an unmet need for patients with mycosis fungoides/Sézary syndrome, a set of incurable diseases.

| S-EPMC7843215 | biostudies-literature

Methyltransferase Inhibitors Restore SATB1 Protective Activity Against Cutaneous T cell Lymphoma

Project description:We report Chromatin Immunoprecipitation for the histone modifications H3K27ac, H3K27m3 and H3K9m3 in human leukemia and lymphoma cell lines HuT78, Jurkat, K562, and RAJI to ascertain the regulatory landscape of in regards to transcriptional repression and activation.

2022-10-26 | GSE159962 | GEO

Discrepancy in SATB1 expression reflects the heterogeneity in cutaneous T cell lymphoma

Project description:SATB1 is an important T-cell specific chromatin organizer in cutaneous T cell lymphoma, while its expression and function in Mycosis fungoides (MF) remain ambiguous. RNA-sequencing was conducted to investigate the genes regulated by SATB1 in MF-derived MJ cells by RNA-sequencing after SATB1-knockdown. With the criteria of P<0.05 and |fold change|>1.3, there were 988 genes upregulated and 1373 genes downregulated in SATB1-silencing MJ cells and further subjected to KEGG analysis. SATB1 silencing in MJ cells showed that SATB1 upregulated genes involved in eosinophil recruitment, including STAT3 and IL13, and downregulated genes in cell cycle progression.

2020-12-31 | GSE144667 | GEO

Mac-1 cells with SATB1 silencing vs control Mac-1 cells

Project description:Transcriptional profiling of primary cutaneous anaplastic large cell lymphoma cell line Mac-1 cells transduced with lenti-virus vector harboring shRNA against SATB1 gene comparing control untreated Mac-1 cells and Mac-1 cells transduced with scrambled shRNA, in which SATB1 expression is not affected. Two condition experiment, SATB1 silenced Mac-1 cells vs control Mac-1 cells. Biological replicates: 2 transduced replicates, 2 control replicates

2013-12-31 | E-GEOD-50916 | biostudies-arrayexpress

Gene Expression Profiling of Cutaneous CD30+ Lymphoproliferative Disorders by RNA-seq

Project description:Cutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs, whereas other CD30+LPDs didn't express SATB1 at all. To elucidate the underlying molecular events in CD30+LPDs with differential SATB1 expression, we subjected 4 SATB1+ and 3 SATB1- CD30+LPDs skin biopsies to second-generation RNA-sequencing (RNA-seq). These data provide a significant resource for studies of CD30+LPDs.

2019-01-25 | GSE109620 | GEO

Mac-1 cells with SATB1 silencing vs control Mac-1 cells

2013-12-31 | GSE50916 | GEO

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. RNA-seq with whild type and knocked-down Satb1

2016-01-13 | E-GEOD-76776 | biostudies-arrayexpress

Satb1

Project description:Satb1

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Discrepancy in SATB1 expression reflects the heterogeneity in cutaneous T cell lymphoma

Project description:Discrepancy in SATB1 expression reflects the heterogeneity in cutaneous T cell lymphoma

| PRJNA604528 | ENA

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

2016-01-13 | GSE76776 | GEO