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Motif-enrichment analysis identified binding sites for XBP1s in Neo-2/15 stimulated BBζ NK cells following co-cultured with AsPC-1 cells

ABSTRACT: Motif-enrichment analysis identified binding sites for XBP1s in Neo-2/15 stimulated BBζ NK cells following co-cultured with AsPC-1 cells

PROVIDER: PRJNA1018231 | ENA |

REPOSITORIES: ENA

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Motif-enrichment analysis identified binding sites for XBP1s in Neo-2/15 stimulated BBζ NK cells following co-cultured with AsPC-1 cells

Project description:Motif-enrichment analysis identified binding sites for XBP1s in Neo-2/15 stimulated BBζ NK cells following co-cultured with AsPC-1 cells, as determined using CUT&TAG-seq, were mainly at the gene encoding nuclear respiratory factor 1 (NRF1)

2023-12-31 | GSE243385 | GEO

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Genome-wide analysis of Xbp1s effect on gene expression in liver by Doxycycline induced TRE-Xbp1s overexpression in mouse

Project description:Analysis of Xbp1s overexpression in liver after 24 hr indution or 48 hr induction in LIXs mouse. As a control, WT mice after 2 hr refeed and 24 hr fast without refeed are used for analysis of postprandial gene expression. This microarray study was used to screen for target genes activated by Xbp1s in liver. Results provide important information for the role of Xbp1s during postprandial. Total RNA obtained from liver tissues from mice on Dox200 chow diet for 24 hr or 48 hr. Mice were fasted for 6 hr before sacrifice for liver.

2013-01-08 | E-GEOD-39301 | biostudies-arrayexpress

Adipocyte XBP1s regulates systemic insulin sensitivity by modulating adiponectin multimerization

Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.

2013-11-21 | E-GEOD-36031 | biostudies-arrayexpress

XBP1s cutnrun

Project description:The unfolded protein response (UPR) has emerged as important signaling pathway mediating anti-viral defenses to Respiratory Syncytial Virus (RSV) infection. In this study, we examine how Inositol Requiring Enzyme (IREa X-Box Binding Protein spliced (XBP1s) arm of the Unfolded Protein Response (UPR) pathway controls the innate response integrating RNA-seq and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) analyses. XBP1s binds to ~4.2 K high-confidence genomic binding sites. Surprisingly these map to only a small subset of IL10/cytokine genes. We further find that that RSV infection enhances XBP1s occupancy on 786 genomic sites enriched in AP1/Fra-1, RELA and SP1 binding sites controlling a core subset of cytokine regulatory factors genes including IFN response factor 1 (IRF1), CSF2, NFKB1A and DUSP10. Selective IRF1 knockdown experiments demonstrates its requirement in control of type I and -III IFNs and IFN-stimulated genes (ISGs) indicating these genes are indirectly regulated through IRF1 transactivation. We conclude that RSV modulates the XBP1 binding complex to the IRF1 epromoter, providing novel insight into how the IRE1-XBP1s pathway potentiates airway mucosal anti-viral responses.

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XBP1s Activation Globally Remodels N-Glycan Structure Distribution Patterns

Project description:The unfolded protein response (UPR), as its name implies, safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated, XBP1s-mediated transcriptional response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s’ transcriptional output for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional consequence of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. XBP1s activity decreases sialylation of tri- and tetra-antennary N-glycans in the HEK293 membrane proteome and secretome, while substantially increasing the population of high mannose N-glycans only in the secretome. Related, but distinctive, signatures in the HEK293 N-glycome are observed when the entire UPR is activated in a stress-dependent manner using thapsigargin. In HeLa cells, stress-independent XBP1s activation increases the population of cell surface high mannose N-glycans and tetra-antennary N-glycans. mRNA profiling experiments suggest that the XBP1s-mediated remodeling of the N-glycome may re-flect a coordinated consequence of transcriptional resculpting of the N-glycan maturation pathway by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s is a master regulator of N-glycan maturation. Moreover, because the sugars on cell surface proteins or on those proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling pathways into al-tered interactions with the extracellular environment.

2018-10-02 | GSE112589 | GEO

Sequencing of AsPC-1 cells with CYP3A5 expression modulation

Project description:Purpose: To understand the transcriptome-wide effect of CYP3A5 knockdown or over-expression in AsPC-1 cells

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MiRNA microarray of overexpression Ctrl and PRLR AsPC-1 cells.

Project description:The study is to explore differentially expressed miRNAs in AsPC-1 cells overexpressing Ctrl or PRLR.

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