ChIP-Seq of in Danio rerio 32hpf embryos for activator transcription factor 3 (atf3)
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Danio rerio
SUBMITTER: Yong Zhou
PROVIDER: E-MTAB-6575 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Cardiomyocytes, the terminally-differentiated contractile cells of the heart, undergo hypertrophic growth in response to endothelin-1. This is associated with changes in mRNA expression of immediate early genes (IEGs). Atf3 is a member of the ATF/CREB family transcription factors which bind as dimers to the cAMP response element (CRE). Atf3 mRNA is particularly associated with cell stress responses and is implicated in negative feedback regulation of gene expression. We confirmed that endothelin-1 promotes expression of Atf3 mRNA and protein in cardiomyocytes and that it is an IEG. Atf3 expression was transient and maximal at 0.5-1 h. We used adenoviruses for expression of antisense Atf3 RNA in cardiomyocytes to inhibit upregulation of Atf3 protein in response to endothelin-1. The effects on the cardiomyocyte transcriptome in control cells and cells exposed to endothelin-1 were examined using Affymetrix rat exon 1.0 ST arrays with data analysis using GeneSpring GX11.5. We identified transcripts that were upregulated by endothelin-1 for which antisense Atf3 significantly (FDR<0.05) enhanced or inhibited expression, respectively. The basal levels of other transcripts that are upregulated by endothelin-1 were also increased by antisense Atf3, though antisense Atf3 had no further effect on the response to endothelin-1. The data were validated by quantitative PCR of selected IEG mRNAs examining the effects at different times.
2012-10-01 | E-MEXP-3392 | biostudies-arrayexpress
Project description:This study shows that in the absence of Atf3, primary mouse macrophages display significantly greater basal and PRR-inducible IFNβ expression. This regulation appears to be directly on the level of Ifnb1 transcription mediated by ATF3 binding proximal to the Ifnb1 promoter under basal condition. The ATF3 expression was demonstrated to be type I IFN-inducible in both human and mouse immune cells. A subset of 36 genes downstream of IFNAR signalling were modulated in an ATF3-dependent manner.The regulation of IFN responses by ATF3 had significant relevance on in vitro viral infection. Together these findings demonstrate that ATF3 is an important regulatory handbrake that limits the magnitude of IFN responses on multiple levels; basal Ifnb1 expression; PRR-inducible IFNβ; and the expression of specific ISGs. 12 samples
2015-09-07 | E-GEOD-61055 | 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.
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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
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2015-08-01 | E-GEOD-60250 | biostudies-arrayexpress
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:DNA binding determination for ATF3 -/- macrophages without stimulation and with stimulation by LPS after 1 or 2 hours.
2006-07-07 | E-MEXP-730 | biostudies-arrayexpress
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.
2014-04-05 | GSE53973 | GEO
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2017-06-30 | GSE81403 | GEO