Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA113645 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted; sites within genes previously identified as STAT3-responsive by microarray analysis. The high percentage of sites able to bind STAT3 in vivo, as assessed by Chromatin Immunoprecipitation (ChIP) analysis, revealed the high predictive power of our method. Experiment Overall Design: Three prototypic situation were investigated using two replications for each experimental point: STAT3+/+ versus STAT3-/- MEFs , STAT3+/+ versus STAT3+/+ treated with OSM and STAT3-/- versus STAT3-/- treated with OSM.
2009-05-16 | E-GEOD-12262 | biostudies-arrayexpress
Project description:Genome-wide binding of STAT3 in peritoneal macrophages
| PRJNA154981 | ENA
Project description:Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4. Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours. ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.
2010-01-08 | E-GEOD-19198 | biostudies-arrayexpress
Project description:Dendritic cells (DC) play a vital role in the induction of activation or tolerance of immune response. STAT3 is a master transcriptional regulator of immune response in DCs by positively or negatively regulating DC function, but the mechanisms are unknown. STAT3 is post-translationally modified by acetylation or phosphorylation. While much is understood about transcriptional targets of phosphorylated STAT3, the gene targets and the functional impact of acetylated-STAT3 remain unclear. We aimed to answer the gene targets of acetylated-STAT3 and test the hypothesis that acetylation of STAT3 plays a key role in negative regulation of DCs. We performed genome-wide binding analysis of acetyl-STAT3 by ChIP-Seq coupled with gene expression microarrays. Acetylation of STAT3 induced by SAHA increased its capability to bind to target DNA sites in genome. Theses binding sites were mostly proximal but some were also distal up to over 100 kb from transcription start site. Gene expression array showed 1701 genes up-regulated and 1668 genes down-regulated. Proximal binding of acety-STAT3 showed more effective transcription function than distal binding. In top 500 binding peaks, the frequency of canonical motifs bound by acetyl-STAT3 were significantly higher than that for noncanonical motifs (p<0.00001). Functional analysis revealed that acetyl-STAT3 regulates target genes by upregulating genes that are primarily involved in negative regulation of cytokine production and IL-10 signaling, or downregulating genes that are primarily involved in immune effector process and antigen processing/presentation. Upregulation of IL-10Ra by acetyl-STAT3 contributes to the enhanced sensitivity of IL-10 signaling and negative regulation of DC function. Bone marrow derived dendritic cells were treated with SAHA (500 nm) or diluent for 12 hours. ChIP was performed using antibodies against STAT3, H3K4me3 and matched IgG control. DNA binding profiles were generated by deep sequencing using Illumina HiSeq 2000.
2015-11-05 | E-GEOD-74262 | biostudies-arrayexpress
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO
Project description:STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted sites within genes previously identified as STAT3-responsive by microarray analysis. The high percentage of sites able to bind STAT3 in vivo, as assessed by Chromatin Immunoprecipitation (ChIP) analysis, revealed the high predictive power of our method.
2009-05-05 | GSE12262 | GEO
Project description:Transcription factor recruitment to genomic sites of action is primarily due to direct protein:DNA interactions. The subsequent recruitment of co-regulatory complexes leads to either transcriptional activation or repression. In contrast to this canonical scheme, some transcription factors such as the glucocorticoid receptor (GR) behave as transcriptional repressors when recruited to target genes through protein tethering. We have investigated the genome-wide prevalence of tethering between GR and Stat3 and found non-reciprocal interactions, namely that GR tethering to DNA-bound Stat3 results in transcriptional repression whereas Stat3 tethering to GR results in synergism. Further, other schemes of GR and Stat3 co-recruitment to regulatory modules result in transcriptional synergism, including neighbouring and composite binding sites. The results indicate extensive transcriptional interactions between Stat3 and GR; further, they provide a genome-wide assessment of transcriptional regulation by tethering and a molecular basis for integration of signals mediated by GR and Stats in health and disease. ChIP-seq analysis of Stat3 and GR binding sites in pituitary corticotroph AtT-20 cell model. Five independant ChIPs were pooled prior library preparation for each contitions: STAT3 (LIF), STAT3 (Dex+LIF), GR (Dex+LIF), GR (Dex) and control IgG.
2012-06-06 | E-GEOD-37235 | biostudies-arrayexpress
Project description:Genome-Wide CRX Binding Sites in adult mouse photoreceptors
| PRJNA130929 | ENA