RNA-Seq in control and TET2 Knockout cells with IFNγ treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132408 | GEO | 2020/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-Seq in control and TET2 Knockout cells with IFNγ treatment
| PRJNA547830 | ENA
Project description:The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about 36 regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identified STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1K285 and JAK1K249. Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This was corroborated by an anticorrelation between STUB1 expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response was increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome.
2022-03-07 | PXD030580 | Pride
Project description:chromatin accessibility (ATAC-seq) experiment. HeLa cells were primed with IFNγ for 24 hours, followed by IFNγ washout. After 48h, naïve and primed cells were induced by IFNγ for 1h and 3h. Cells were harvested at indicated time points and processed for ATAC-seq.
2023-05-06 | E-MTAB-12624 | biostudies-arrayexpress
Project description:Loss-of-function TET2 mutations (TET2MT) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2MT thus result in hypermethylation and transcriptional repression. Ascorbic acid (AA) increases dioxygenase activity by facilitating Fe(III)/Fe(II) redox reaction and may alleviate some biological consequences of TET2MT by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of TET2MT MN, clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of TET2MT. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I/II HDAC inhibitor or sirtuin activators in TET2MT leukemia.
2020-09-09 | PXD020550 | Pride
Project description:STAT1 and IRF1 transcription factor enrichment by CUT&RUN. HeLa cells were primed with IFNγ for 24 hours, followed with IFNγ washout. After 48h, naïve and primed cells were induced by IFNγ for 1h and 3h. Cells were harvested at indicated time points and processed for CUT&RUN
2023-05-06 | E-MTAB-12625 | biostudies-arrayexpress
Project description:Tet2 regulates gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine. Profiling the genomic locations of 5-hydroxymethylcytosine after Tet2 manipulation can inform us of the targets of Tet2 regulation. We profiled hydroxymethylcytosine in Tet2 knockout neurons to determine the targets of Tet2 in neurons.
2023-03-25 | GSE199597 | GEO
Project description:Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. In this study, we revealed a role for Tet2 in sustaining the immunosuppressive function of tumor-tissue myeloid cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients, and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo, and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function. This resulted in increased numbers of effector T cells in the tumor, and T cell depletion abolished the reduced tumor growth observed upon myeloid-specific deletion of Tet2. Our findings reveal a non-cell-intrinsic, tumor-promoting function for Tet2, and suggest that Tet2 may present a therapeutic target for the treatment of non-hematologic malignancies.
2017-08-15 | GSE98964 | GEO
Project description:we compared self-renewal and lineage specification of WT and Tet2-deficient HSPCs during ageing and demonstrated that Tet2 ablation alters age-dependent HSC functional decline, revealing a disparate ageing process in the Tet2-deficient haemopoietic system.
2023-08-11 | GSE183675 | GEO
Project description:we compared self-renewal and lineage specification of WT and Tet2-deficient HSPCs during ageing and demonstrated that Tet2 ablation alters age-dependent HSC functional decline, revealing a disparate ageing process in the Tet2-deficient haemopoietic system.
2023-09-10 | GSE157592 | GEO
Project description:Estrogen receptor-alpha (ER) drives tumour development and metastasis in ER positive (ER+) breast cancer. GATA3 is a transcription factor that has been closely linked to ER function, but the role of GATA3 in ER-transcriptional activity is not clear. We sought to identify the contribution of GATA3 to the ER complex, by conducting quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME), to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, very few proteins were dissociated from the ER complex in the absence of GATA3, with the only major change being loss of TET2 in the ER complex. In breast cancer cells and Patient-Derived Xenograft (PDX) tissue, TET2 binding events were shown to constitute a near-total subset of ER binding events, and loss of TET2 was functionally associated with reduced activation of proliferative pathways. To investigate the TET2-ER relationship, the role of TET2 in regulating DNA modifications in ER+ breast cancer cells was examined. TET2 knockdown did not appear to result in changes to global DNA methylation, however, oxidation of methylated DNA to 5-hydroxymethylcytosine (5hmC) was significantly reduced after TET2 depletion and these events occurred at ER enhancers. These findings implicate TET2 in the production and maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.
2021-02-10 | PXD019438 | Pride