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ChIP-Seq of TRIB3 and ATF4 in HepG2 cells treated with bortezomib

ABSTRACT: ChIP-Seq of TRIB3 and ATF4 in HepG2 cells treated with bortezomib

PROVIDER: PRJNA702470 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13732757.fastq.gz	Fastqsanger.gz
	SRR13732758.fastq.gz	Fastqsanger.gz
	SRR13732759.fastq.gz	Fastqsanger.gz
	SRR13732760.fastq.gz	Fastqsanger.gz
	SRR13732761.fastq.gz	Fastqsanger.gz

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Similar Datasets

ChIP-Seq of TRIB3 and ATF4 in HepG2 cells treated with bortezomib

Project description:The proteasome is an appealing anti-cancer drug target and the proteasome inhibitor bortezomib has been approved for the treatment of certain types of malignancies. However, the molecular mechanisms underlying cancer cell resistance to bortezomib remain poorly understood. The pseudokinase TRIB3, an inhibitor of ATF4, is expressed at a high basal level in hepatoma cells and is strongly upregulated in response to bortezomib. To map genome-wide chromatin binding loci of TRIB3 protein, we fused a Flag tag to endogenous TRIB3 in HepG2 cells and performed ChIP-Seq. The results demonstrate that TRIB3 predominantly colocalizes with ATF4 on chromatin and the proteins reside in genomic regions containing the C/EBP-ATF motif. Bortezomib treatment leads to a robust enrichment of TRIB3 binding near genes induced by bortezomib and involved in the ER stress response and cell death. Disruption of TRIB3 increases C/EBP-ATF-driven transcription, augments ER stress and cell death in cells exposed to bortezomib, while TRIB3 overexpression enhances the cell survival. Thus, TRIB3, colocalizing with ATF4 and limiting its transcriptional activity, functions as a factor increasing resistance to bortezomib, while pharmacological over-activation of eIF2alpha-ATF4 can overcome the endogenous restraint mechanisms and sensitize cells to bortezomib.

2021-05-24 | GSE166958 | GEO

Gene expression profiling of HepG2 cell response to bortezomib in combination with nelfinavir or ISRIB, compounds targeting the eIF2a-ATF4 pathway

Project description:We investigate how modulation of the eIF2alpha-ATF4 stress pathway affects hepatoma cell response to bortezomib. Transcriptome profiling revealed that many ATF4 transcriptional target genes are among the highest upregulated genes in bortezomib-treated HepG2 human hepatoma cells. While pharmacological enhancement of the eIF2alpha-ATF4 pathway activity results in the elevation of the activities of all branches of the unfolded protein response (UPR) and sensitizes cells to bortezomib toxicity, the suppression of ATF4 induction delays bortezomib-induced cell death. The pseudokinase TRIB3, an inhibitor of ATF4, is expressed at a high basal level in hepatoma cells and is strongly upregulated in response to bortezomib. Bortezomib treatment leads to a robust enrichment of TRIB3 binding near genes induced by bortezomib and involved in the ER stress response and cell death. Disruption of TRIB3 increases C/EBP-ATF-driven transcription, augments ER stress and cell death in cells exposed to bortezomib, while TRIB3 overexpression enhances the cell survival. Thus, TRIB3, colocalizing with ATF4 and limiting its transcriptional activity, functions as a factor increasing resistance to bortezomib, while pharmacological over-activation of eIF2alpha-ATF4 can overcome the endogenous restraint mechanisms and sensitize cells to bortezomib.

2021-05-24 | GSE166923 | GEO

Gene expression profiling of the effect of elevated TRIB3 expression on the transcriptional response to glucose deprivation

Project description:Gene expression profiling of HEK293-derived cell lines that are stably transfected with either a tetracycline-inducible TRIB3 expression construct (TRIB3-293 cells), tetracycline-inducible ATF4 expression construct (ATF4-293 cells) or the corresponding empty vector (Vector-293 cells). Samples from tetracycline-treated and tetracycline-untreated cell cultures were collected after a 24-hour (TRIB3-293 cells, Vector-293) or 4-hour (ATF4-293) incubation in growth medium either with or without glucose.

2016-02-09 | E-MTAB-3318 | biostudies-arrayexpress

Gene expression profile in human hepatoma HepG2 cells induced by gambogic acid and bortezomib

Project description:This experiment is designed to evaluate gene expression alterations following treatment with gambogic acid and bortezomib in human HepG2 cells. We find gambogic acid yielded a similar gene expression profile as did bortezomib. Total RNA were extracted from human HepG2 cancer cells treated with gambogic acid (0.25μM, 0.5μM, 0.75μM) or bortezomib (50nM) for 9hr. HepG2 cells treated with vehicle alone was used as a control.

2012-06-14 | E-GEOD-38730 | biostudies-arrayexpress

Gene expression profile in human hepatoma HepG2 cells induced by gambogic acid and bortezomib

2012-06-15 | GSE38730 | GEO

Gene expression profiling of HepG2 cell response to bortezomib in combination with nelfinavir or ISRIB, compounds targeting the eIF2a-ATF4 pathway

Project description:Gene expression profiling of HepG2 cell response to bortezomib in combination with nelfinavir or ISRIB, compounds targeting the eIF2a-ATF4 pathway

| PRJNA702297 | ENA

Transcription profiling of human cell cancer line treated with bortezomib or Eeyarestatin I (EerI) reveals ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3 only protein NOXA in cancer cells

Project description:The ubiquitin-proteasome system (UPS) has recently emerged as a major target for drug development in cancer therapy. The proteasome inhibitor bortezomib has clinical activity in multiple myeloma and mantle cell lymphoma. Here we report that Eeyarestatin I (EerI), a chemical inhibitor that blocks ER-associated protein degradation (ERAD), has anti-tumor and biologic activities similar to bortezomib, and can synergize with bortezomib. Like bortezomib, EerI-induced cytotoxicity requires the upregulation of the BH3 only pro-apoptotic protein NOXA. We further demonstrate that both EerI and bortezomib activate NOXA via an unanticipated mechanism that requires cooperation between two processes: First, these agents elicit an integrated stress response program at the ER to activate the CREB/ATF transcription factors ATF3 and ATF4. We show that ATF3 and ATF4 form a complex capable of binding to the NOXA promoter, which is required for NOXA activation. Second, EerI and bortezomib also block ubiquitination of histone H2A to relieve its inhibition on NOXA transcription. Our results identify a class of anti-cancer agents that integrate ER stress response with an epigenetic mechanism to induce cell death. Experiment Overall Design: 1. EerI 10 vs 0 Experiment Overall Design: 2. EerI 10 vs 0 Experiment Overall Design: 3. Bzm 10 vs 0 Experiment Overall Design: 4. Bzm 10 vs 0

2009-02-28 | E-GEOD-14003 | biostudies-arrayexpress

Pharmacological or TRIB3-Mediated Suppression of ATF4 Transcriptional Activity Promotes Hepatoma Cell Resistance to Proteasome Inhibitor Bortezomib.

Project description:The proteasome is an appealing target for anticancer therapy and the proteasome inhibitor bortezomib has been approved for the treatment of several types of malignancies. However, the molecular mechanisms underlying cancer cell resistance to bortezomib remain poorly understood. In the current article, we investigate how modulation of the eIF2α-ATF4 stress pathway affects hepatoma cell response to bortezomib. Transcriptome profiling revealed that many ATF4 transcriptional target genes are among the most upregulated genes in bortezomib-treated HepG2 human hepatoma cells. While pharmacological enhancement of the eIF2α-ATF4 pathway activity results in the elevation of the activities of all branches of the unfolded protein response (UPR) and sensitizes cells to bortezomib toxicity, the suppression of ATF4 induction delays bortezomib-induced cell death. The pseudokinase TRIB3, an inhibitor of ATF4, is expressed at a high basal level in hepatoma cells and is strongly upregulated in response to bortezomib. To map genome-wide chromatin binding loci of TRIB3 protein, we fused a Flag tag to endogenous TRIB3 in HepG2 cells and performed ChIP-Seq. The results demonstrate that TRIB3 predominantly colocalizes with ATF4 on chromatin and binds to genomic regions containing the C/EBP-ATF motif. Bortezomib treatment leads to a robust enrichment of TRIB3 binding near genes induced by bortezomib and involved in the ER stress response and cell death. Disruption of TRIB3 increases C/EBP-ATF-driven transcription, augments ER stress and cell death upon exposure to bortezomib, while TRIB3 overexpression enhances cell survival. Thus, TRIB3, colocalizing with ATF4 and limiting its transcriptional activity, functions as a factor increasing resistance to bortezomib, while pharmacological over-activation of eIF2α-ATF4 can overcome the endogenous restraint mechanisms and sensitize cells to bortezomib.

| S-EPMC8150958 | biostudies-literature

The effect of TRIB3 overexpression on mouse hepatocytes

Project description:To investigate the effect of TRIB3 overexpression on regulation of lipid metabolism in hepatocytes, we isolated mouse primary hepatocytes from AAV-GFP or AAV-Trib3 mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of two groups of mouse primary hepatocytes from AAV-GFP or AAV-Trib3 mice.

2023-05-28 | GSE232807 | GEO

Genome-wide analysis of ATF4 binding in histidinol-treated cells

Project description:Activating Transcription Factor 4 (ATF4) is a transcription factor induced by the integrated stress response (ISR). This experiment is a genome-wide occupancy profiling of ATF4 in human HAP1 cells. HAP1 is a near-haploid human cell line that was derived from KBM-7 cells isolated from a patient with Chronic Myelogenous Leukemia. We induced ATF4 expression by mimicking amino acid starvation with the drug histidinol. We identified peaks of ATF4 binding using three independent antibodies. Examination of ATF4 binding in HAP1 cells treated with 2 mM histidinol for 24 hours.

2015-08-28 | E-GEOD-69304 | biostudies-arrayexpress

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