Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation [ChIP-Seq]
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ABSTRACT:
PROVIDER: PRJNA679181 | ENA |
REPOSITORIES: ENA
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Project description:Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation
| PRJNA679186 | ENA
Project description:We provide a set of genes that are directly bound by Dhx9 in CD8 T cells from LCMV infected mice.
2020-11-19 | GSE161694 | GEO
Project description:Nuclear sensor molecules of innate cells recognize pathogenic DNA or RNA to activate innate immunity and defense against bacteria and virus infection. Although some sensors exhibit their preliminary functions in T cells, it is still unclear about the underlying mechanism. Here we found a nuclear sensor-Dhx9, was enhanced its expression in effector CD8 T cells. T cell specific deletion of Dhx9 caused an impaired CD8 T cell expansion, memory formation and virus clearance. Mechanically, Dhx9 could directly regulate id2 transcription and in turn control effector CD8 T cell differentiation. Importantly, Dhx9 could bind to Lck protein, mediate Zap70 phosphorylation, and promoting TCR downstream signaling - ERK pathway to protect effector CD8 T cells from apoptosis. The DSRM and DEXDc-Helicase domain is required for Lck binding and Id2 transcription, respectively. Therefore, we revealed a novel regulatory mechanism that innate nuclear sensor regulates T cell fate and function through modulating adaptive pathways.
2020-11-19 | GSE161697 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-19 | GSE161698 | GEO
Project description:Dhx9 controls effector CD8 T cell differetiation program
| PRJNA678442 | ENA
Project description:We provide differentially gene expression between wt and Dhx9-/- CD8 T cells from LCMV infected mice.
2020-11-15 | GSE161489 | GEO
Project description:The ATP-dependent DExH/D-box helicase DHX9 is a key participant in a number of gene regulatory steps, including transcriptional, translational, microRNA-mediated control, DNA replication, and maintenance of genomic stability. DHX9 has also been implicated in maintenance of the tumorigenic process and in drug response. Here, we report that inhibition of DHX9 expression is lethal to multiple human and mouse cancer cell lines. In contrast, using a novel conditional shDHX9 mouse model, we demonstrate that sustained and prolonged suppression of DHX9 is well tolerated at the organismal level. Our results demonstrate a robust tolerance for DHX9 knockdown in non-transformed cells and supports the targeting of DHX9 as an effective and specific chemotherapeutic approach. Comparison of gene expression in large intestine of mice with or without reduced expression of DHX9.
2016-05-19 | E-GEOD-76765 | biostudies-arrayexpress
Project description:R-loops, which consist of a DNA/RNA hybrid and a displaced single-stranded DNA (ssDNA), are increasingly recognized as critical regulators of chromatin biology. R-loops are particularly enriched at gene promoters, where they play important roles in regulating gene expression. However, the molecular mechanisms that control promoter-associated R-loops remain unclear. The epigenetic “reader” Tudor domain-containing protein 3 (TDRD3), which recognizes methylarginine marks on histones and on the C-terminal domain of RNA polymerase II, was previously shown to recruit DNA topoisomerase 3B (TOP3B) to relax negatively supercoiled DNA and prevent R-loop formation. Here, we further characterize the function of TDRD3 in R-loop metabolism and introduce the DExH-box helicase 9 (DHX9) as a novel interaction partner of the TDRD3/TOP3B complex. TDRD3 directly interacts with DHX9 via its Tudor domain. This interaction is important for recruiting DHX9 to target gene promoters, where it resolves R-loops in a helicase activity-dependent manner to facilitate gene expression. Additionally, TDRD3 also stimulates the helicase activity of DHX9. This stimulation relies on the OB-fold of TDRD3, which likely binds the ssDNA in the R-loop structure. Thus, DHX9 functions together with TOP3B to suppress promoter-associated R-loops. Collectively, these findings reveal new functions of TDRD3 and provide important mechanistic insights into the regulation of R-loop metabolism.
2021-06-26 | GSE178905 | GEO
Project description:Sensing of double-stranded RNA (dsRNA) is an important component of innate immunity. Proteins like PKR and MDA5 recognize dsRNA and activate various pathways to fight viral infection. In addition to viral dsRNA, many endogenous RNAs containing double-stranded regions can be misrecognized as immunogenic. The RNA editing enzyme ADAR1, specifically its p150 isoform, has been shown to suppress activation of PKR and MDA5 through its A-to-I editing activity. While the cytoplasmic ADAR1-p150 isoform has been well established within this role, the functions of the nuclear ADAR1-p110 isoform are less understood. To address this knowledge gap, we utilized proximity labeling by APEX2 to identify putative ADAR1-p110 interacting proteins. We identified 110 proteins across three breast cancer cell lines that either interact with p110 or are within close proximity. Many of these proteins have known roles in RNA metabolism. Nine of the identified proteins belong to the DEAD or DEAH box families of RNA helicases, including DHX9. DHX9 is overexpressed in breast cancer, with expression closely correlated with that of p110. By co-immunoprecipitation we confirmed that p110 interacts with DHX9. Knockdown of DHX9 in several triple-negative breast cancer cell lines caused cell death and activation of the dsRNA sensor PKR. In two cell lines that are refractory to knockdown of ADAR1, the combined knockdown of DHX9 and ADAR1 caused a substantial increase in PKR activity, where knockdown of either alone had no effect. Knockdown of DHX9 and ADAR1 caused activation of the type I IFN pathway, RNase L and NF-KB signaling. Activation of these proteins and pathways was not seen with individual knockdown of ADAR1 or DHX9. Activation of PKR following combined knockdown of ADAR1 and DHX9 could be rescued by expression of p110, p150, DHX9, and catalytically inactive DHX9. Additionally PKR activation could be rescued by the dsRBM of DHX9, revealing an important role for dsRBMs in suppressing PKR activation. Together these results reveal an important role for DHX9 in suppressing dsRNA sensing by multiple pathways.
2023-08-07 | GSE224677 | GEO
Project description:In our study, we valided DHX9 and NPM1 interact with KIMAT1, whereas DHX9 also interacts with HIF1A-As2. DHX9 is a highly conserved DEAD-box protein expressed in the nucleus and the cytoplasm, involved in many processes including transcriptional activation, miRNA biogenesis and tumor cell maintenance. NPM1 is predominantly localized in the nucleoplasm, where it associates with active RNA polymerase II and transcriptionally activates genes involved in cancer. We silenced DHX9 and NPM1 and performed RNA-seq to examine the dysregulated genes by DHX9 and NPM1.
2020-12-17 | GSE124626 | GEO