Identification of Hepatic Genes Regulated by ATF3 using Next Generation Sequencing
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PROVIDER: PRJNA623854 | ENA |
REPOSITORIES: ENA
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Project description:This study aimed to investigate how many genes were regulated by hepatocyte ATF3. C57BL/6J mice were injected intravenously with adeno-associated virus (AAV) expressing human activating transcription factor 3 (ATF3) under the control of an albumin promoter (AAV8-ALB-ATF3) or AAV8-ALB-Null). After 8 weeks, liver samples were used for RNA sequencing using Illumina NextSeq 500. Over 3000 genes were found to be up- or down-regulated by ATF3.
2020-11-26 | GSE148301 | GEO
Project description:A cross-species analysis identified MELK as a potential therapeutic target in prostate cancer. To further elucidate the functional role of MELK in prostate cancer cells, we aimed to identify MELK-regulated genes. C4-2b cells were either treated with a small-molecule MELK inhibitor (OTSSP167), or transfected with siRNAs targeting MELK. Differentially expressed genes were identified using next-generation sequencing. Our results demonstrate that MELK promotes the expression of genes associated with tumour progression in prostate cancer cells.
2018-02-05 | GSE94570 | GEO
Project description:The goal of this study is to identify genes that are regulated by activiating transcription factor (ATF3) in the cellular response to serine deprivation. Serine biosynthesis is crucial for cancer cells to proliferate and survival under serine-limiting conditions. We found that ATF3 expression induced by serine deprivation supports cancer cell growth. This RNA-seq study is thus designed to understand how ATF3 regulates serine biosynthesis in cells. The results indicate that ATF3 regulates the genes involved in the serine synthesis pathway.
2021-11-09 | GSE164850 | GEO
Project description:Expression of the activating transcription factor 3 (ATF3) gene is induced by Toll-like receptor (TLR) signaling. In turn, ATF3 protein inhibits the expression of various TLR-driven pro-inflammatory genes. Given its counter-regulatory role in diverse innate immune responses, we defined the effects of ATF3 on neutrophilic airway inflammation in mice. ATF3 deletion was associated with increased lipopolysaccharide (LPS)-driven airway epithelia production of CXCL1, but not CXCL2, findings concordant with a consensus ATF3-binding site identified solely in the Cxcl1 promoter. Unexpectedly, ATF3-deficient mice did not exhibit increased airway neutrophilia after LPS challenge. Bone marrow chimeras revealed a specific reduction in ATF3-/- neutrophil recruitment to wild type lungs. In vitro, ATF3-/- neutrophils exhibited a profound chemotaxis defect. Global gene expression analysis identified ablated Tiam2 expression in ATF3-/- neutrophils. TIAM2 regulates cellular motility by activating Rac1-mediated focal adhesion disassembly. Notably, ATF3-/- and ATF3-sufficient TIAM2 knockdown neutrophils, both lacking TIAM2, exhibited increased focal complex area, along with excessive CD11b-mediated F-actin polymerization. Together, our data describe a dichotomous role for ATF3-mediated regulation of neutrophilic responses: inhibition of neutrophil chemokine production, but promotion of neutrophil chemotaxis. Ly6G+ neutrophils were purified by magnetic beads from WT or ATF3 KO bone marrow and RNA was immediately isolated for global gene expression using microarrays.
2014-04-05 | E-GEOD-53973 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to generate transcriptome profiling (RNA-seq) of AT2 cells with over expression of Atf3 and Thra. Methods: AT2 cell mRNA profiles of 5 or 6-week-old wild-type mice were generated by deep sequencing, in triplicate. The Illumina Nextseq 500 system was used to generate raw data at 75 cycles. Fastq files was aligned to the reference genome and DEseq2 was used to analyze the differentially expressed genes. Results: Our results show that Atf3 or Thra overexpression promotes the expression of genes associated AT2 cell proliferation. Conclusions: Our study represents the first detailed analysis of transcriptomes of mouse AT2 cell with Atf3 or Thra overexpression, with biologic replicates, generated by RNA-seq technology.
2022-07-21 | GSE183129 | GEO
Project description:Cancer associated fibroblasts (CAFs) play an important role in initiating and promoting epithelial cancers. The specific chromatin modifications involved in CAF activation remain to be elucidated. CSL, a constitutive transcriptional repressor and mediator of canonical Notch signaling, functions as a direct negative regulator of CAF effector genes and suppresses cancer/stromal cell expansion. We find that ATF3, a key stress responsive transcriptional repressor up-regulated in the acute UVA response of skin fibroblasts, is down-modulated in stromal cells of premalignant skin SCC lesions similarly to CSL. Increased ATF3 expression counteracts the consequences of compromised CSL, binding to a large set of overlapping target genes. At low basal levels, ATF3 converges with CSL in negative control of CAF activation, binding to a very small number of genomic loci that encompass mostly non-coding RNAs and pseudogenes. Silencing of ATF3 results in chromatin modifications and Pol II recruitment to many loci to which ATF3 does not bind, which are similarly affected by CSL silencing. The observed changes are of functional significance, as Bet inhibitors, which unlink activated chromatin from the basic transcription apparatus, have opposite effects of ATF3 or CSL silencing on all tested CAF effector genes. They exert a similar impact on clinically-derived CAFs both in vitro and upon topical in vivo treatment. Thus, ATF3 converges with CSL in global chromatin control of CAF activation with their loss eliciting epigenetic changes amenable to cancer and stroma-focused intervention.
2017-06-30 | GSE81403 | GEO
Project description:Maintenance of genetic integrity is essential for survival of all organisms. Activating transcription factor 3 (ATF3) is a member of the c-AMP response element binding (CREB)/ATF family of transcription factors, and is highly inducible by various stress conditions including DNA damage. However, downstream targets and molecular basis underlying pleiotropic effects of ATF3 on the cell fate have been largely unknown. To identify ATF3 targets in the human genome, we carried out chromatin immunoprecipitation-microarray (ChiP-on-chip) and knockdown-expression profiling analysis using two models where ATF3 was either transiently induced or constitutively expressed. We show that ATF3 binds to an unexpectedly large number of targets; 5,984 promoters in HCT116 cells treated with an alkylating agene methyl methanesulfonate (MMS) and 1,423 promoters in LNCaP cells constitutively expressing ATF3. Importantly, targets of MMS-induced ATF3 are highly enriched not only for CREB/ATF motifs but also for binding sites of several stress sensors including DDIT3/CHOP, Egr1, and c-Ets which are concomitantly induced by MMS. Stress-induced ATF3 affects broad but select biological processes including cell cycle, cell death, adhesion, biosynthesis, and receptor signaling pathways. In addition, ATF3 binds to as many as 40% of the p53 targets and preferentially enhances MMS-induced activation of proapoptotic genes such as DR4, DR5, and PUMA, consistent with the proapoptotic effect of ATF3. These data shed new light on the co-regulatory function of ATF3 in the stress-induced transcription factor network. The comprehensive list of genomic targets of ATF3 will facilitate further understanding the role of ATF3 in determining life and death of cells under both physiological and tumour-associated stress conditions. Maintenance of genetic integrity is fundamental to survival of all organisms. DNA damage can be caused by various agents in environment and elicits complex responses in the cell. ATF3 is one of the transcription factors activated by various stress conditions including DNA damage, and has been shown to have pleiotropic effects on life and death of cells depending on the context of experimental conditions. It has been largely unknown, however, which genes and pathways are regulated by stress-induced ATF3. Here we attempted to answer this question by chromatin immunoprecipitation-microarray analysis of downstream targets of ATF3. We show that ATF3 binds to an unexpectedly large number of promoters (nearly 6,000) in a human colorectal cancer cell lineHCT116 treated with an alkylating agent methyl methanesulfonate. Interestingly, the ATF3 targets are highly enriched for binding sites of other stress sensors shedding light on a transcriptional co-regulatory network of DNA damage response. We further show that ATF3 regulates expression of genes in select biological processes including cell cycle, cell death, adhesion, metabolism, signal transduction, and the p53 pathway. The comprehensive list of ATF3 targets provides new insight into a highly inter-connected network of stress-induced transcription factors around ATF3. ChIP-chip samples: Comparison of ATF3-IP and whole genome DNA (control) Gene expression samples: HCT116 cells pre-transfected with either control siRNA or ATF3 knockdown siRNA and stimulated by methyl methanesulfonate (MMS) for 0, 6, 12, and 24 hours
2010-10-01 | E-GEOD-18457 | biostudies-arrayexpress
Project description:Aim: Hepatic fibrosis is a major worldwide medical problem and can develop into liver cirrhosis and hepatocellular carcinoma(HCC). Until now, there are no effective drugs for liver ?brosis because the molecular mechanism of progression of liver fibrosis is not fully understood. MicroRNAs (miRNAs) are an important class of small non-coding functional RNAs that play a key role in many biological processes. The purpose of this study was to clarify how the aberrant expression of miRNAs participates in development of the liver fibrosis in rat liver fibrosis model. Methods: Fibrotic and paired normal liver tissues were collected and assesssed by deep sequencing technology. MiRNA pro?ling results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics was used to predict miRNA targets. Results: Nine deregulated miRNAs were induced in porcine serum (PS)-induced hepatic fibrosis versus normal liver. Further analysis revealed several signaling pathways (e.g., gap junction and neuroactive ligand-receptor interaction) may be associated with hepatic fibrogenesis. Conclusion: Several miRNAs are dysregulated in PS-induced hepatic fibrosis and seem to be closely associated with hepatic fibrogenesis. These results provide an experimental basis for understanding the mechanism of hepatic fibrosis. We sequenced two samples, including case and control. Each sample has two replicates.
2015-06-04 | E-GEOD-54028 | biostudies-arrayexpress
Project description:Cancer-host interactions play an important role in cancer development. We identified ATF3, an adaptive-response gene, in the host to facilitate metastasis. We also demonstrated that the macrophage is one of the key cell types for host-ATF3 to function. Furthermore, matrix metalloproteases 9 is a functionally important target gene of ATF3 in co-culture assays. Gene profiling with bioinformatics analyses indicated that ATF3 downstream gene-signatures derived from tumor-associated macrophages in a mouse model can distinguish human tumor stroma from M-bM-^@M-^\distantM-bM-^@M-^] stroma in and can stratify the patients into high- versus low-risk groups. Importantly, multivariate analyses indicated that high expression of ATF3 itself in mononuclear cells within breast tumors is an independent predictor for breast cancer-specific death in a cohort of patients. Approximately 21 days after orthotopic injection of PyMT breast cancer cells into syngeneic C57BL/6 mice (WT or ATF3 KO hosts) tumors were removed (tumors were ~1 cm cubic in volume), enzymatically digested to generate single cell suspensions, stained, and sorted for F4/80 and CD45 double positive cells by FACS. Isolated cells were lysed in TRIzol, processed to generate total RNA, and gene expression analyzed by microarray. Four replicate WT TAM samples and four replicate ATF3 KO TAM samples were analyzed.
2013-07-10 | E-GEOD-36904 | biostudies-arrayexpress
Project description:We performed ChIP-seq to find the trageted genes regulated by ATF3 in hypoxia/reoxygenation (H/R)using ATF3 antibody for ChIP.
2023-01-01 | GSE193996 | GEO