Uncovering early response of gene regulatory networks in ES cells by systematic induction of transcription factors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE16375 | GEO | 2009/10/01
SECONDARY ACCESSION(S): PRJNA115329
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE14559: Timed induction of 50 transcription factors in ES cells reveals a common mechanism to initiate differentiations GSE14586: Cdx2 Binding Sites On Cdx2 Expressing ES Cells GSE16148: Timed induction of 10 transcription factors - ES time series data Refer to individual Series
2009-09-30 | E-GEOD-16375 | biostudies-arrayexpress
Project description:To examine transcription factor (TF) network(s), we created mouse ESC lines, in each of which 1 of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracycline-repressible locus. Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes. By contrast, genes downregulated by CDX2 did not show CDX2 binding but were enriched with binding sites for POU5F1, SOX2, and NANOG. Genes with binding sites for these core TFs were also downregulated by the induction of at least 15 other TFs, suggesting a common initial step for ESC differentiation mediated by interference with the binding of core TFs to their target genes. These ESC lines provide a fundamental resource to study biological networks in ESCs and mice.
| S-EPMC2770715 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important miRNAs in GBM and, potentially, other cancers.
| S-EPMC3400583 | biostudies-literature
Project description:Here we report the generation and characterization of 84 mouse ES cell lines with doxycycline-controllable transcription factors (TFs) which, together with the previous 53 lines, cover 7-10% of all TFs encoded in the mouse genome. Global gene expression profiles of all 137 lines after the induction of TFs for 48 hrs can associate each TF with the direction of ES cell differentiation, regulatory pathways, and mouse phenotypes. These cell lines and microarray data provide building blocks for a variety of future biomedical research applications as a community resource.
| S-EPMC3240988 | biostudies-literature
Project description:BackgroundTranscription regulatory networks are composed of interactions between transcription factors and their target genes. Whereas unicellular networks have been studied extensively, metazoan transcription regulatory networks remain largely unexplored. Caenorhabditis elegans provides a powerful model to study such metazoan networks because its genome is completely sequenced and many functional genomic tools are available. While C. elegans gene predictions have undergone continuous refinement, this is not true for the annotation of functional transcription factors. The comprehensive identification of transcription factors is essential for the systematic mapping of transcription regulatory networks because it enables the creation of physical transcription factor resources that can be used in assays to map interactions between transcription factors and their target genes.ResultsBy computational searches and extensive manual curation, we have identified a compendium of 934 transcription factor genes (referred to as wTF2.0). We find that manual curation drastically reduces the number of both false positive and false negative transcription factor predictions. We discuss how transcription factor splice variants and dimer formation may affect the total number of functional transcription factors. In contrast to mouse transcription factor genes, we find that C. elegans transcription factor genes do not undergo significantly more splicing than other genes. This difference may contribute to differences in organism complexity. We identify candidate redundant worm transcription factor genes and orthologous worm and human transcription factor pairs. Finally, we discuss how wTF2.0 can be used together with physical transcription factor clone resources to facilitate the systematic mapping of C. elegans transcription regulatory networks.ConclusionwTF2.0 provides a starting point to decipher the transcription regulatory networks that control metazoan development and function.
| S-EPMC1414109 | biostudies-literature
Project description:Biological networks are complex (non-linear), redundant (cyclic) and compartmentalized at the subcellular level. Rational manipulation of plant metabolism may have failed due to inherent difficulties of a comprehensive understanding of regulatory loops. We first need to identify key factors controlling the regulatory loops of primary metabolism. The paradigms of plant networks are revised in order to highlight the differences between metabolic and transcriptional networks. Comparison between animal and plant transcription factors (TFs) reveal some important differences. Plant transcriptional networks function at a lower hierarchy compared to animal regulatory networks. Plant genomes contain more TFs than animal genomes, but plant proteins are smaller and have less domains as animal proteins which are often multifunctional. We briefly summarize mutant analysis and co-expression results pinpointing some TFs regulating starch enzymes in plants. Detailed information is provided about biochemical reactions, TFs and cis regulatory motifs involved in sucrose-starch metabolism, in both source and sink tissues. Examples about coordinated responses to hormones and environmental cues in different tissues and species are listed. Further advancements require combined data from single-cell transcriptomic and metabolomic approaches. Cell fractionation and subcellular inspection may provide valuable insights. We propose that shuffling of promoter elements might be a promising strategy to improve in the near future starch content, crop yield or food quality.
| S-EPMC6625501 | biostudies-literature
Project description:Networks of transcription factors (TFs) are thought to determine and maintain the identity of cells. Here we systematically repressed each of 100 TFs with shRNA and carried out global gene expression profiling in mouse embryonic stem (ES) cells. Unexpectedly, only the repression of a handful of TFs significantly affected transcriptomes, which changed in two directions/trajectories: one trajectory by the repression of either Pou5f1 or Sox2; the other trajectory by the repression of either Esrrb, Sall4, Nanog, or Tcfap4. The data suggest that the trajectories of gene expression change are already preconfigured by the gene regulatory network and roughly correspond to extraembryonic and embryonic fates of cell differentiation, respectively. These data also indicate the robustness of the pluripotency gene network, as the transient repression of most TFs did not alter the transcriptomes.
| S-EPMC3589720 | biostudies-literature
Project description:To decipher the structure and behaviors of the transcription factor (TF) network, we created 50 permanent mouse ES cell lines, in each of which one of the 50 transcription factors tagged with FLAG, is inserted into the doxycycline (dox)-repressible ROSA26 locus. We have obtained time series data for 10 of the transcripts at 24h,48h and 72hr. Expression profiling reveals Cdx2 as the most potent inducer of transcriptome perturbation in ES cells, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. Immunoprecipitation (IP) with a FLAG-antibody in Cdx2-induced ES cells, identifies NuRD in CDX2-associated protein complexes; and chromatin-IP-sequencing identifies CDX2-binding sites predominantly in genes up-regulated by CDX2. Compendium analyses of Cdx2- and the other TF-inducible ES cells suggest a central role of the POU5F1/SOX2/NANOG protein complex in a swift-acting control mechanism to down-regulate a common set of genes at the beginning of multi-lineage ES cell differentiations. These ES cell lines will be a valuable resource to study biological networks in ES cells and mice. Keywords: dose response design,genetic modification design,individual genetic characteristic design,reference design,replicate design,time series design
2009-10-01 | GSE16148 | GEO
Project description:The commitment of germ cells to either oogenesis or spermatogenesis occurs during fetal gonad development: germ cells enter meiosis or mitotic arrest, depending on whether they reside within an ovary or a testis, respectively. Despite the critical importance of this step for sexual reproduction, gene networks underlying germ cell development have remained only partially understood. Taking advantage of the W(v) mouse model, in which gonads lack germ cells, we conducted a microarray study to identify genes expressed in fetal germ cells. In addition to distinguishing genes expressed by germ cells from those expressed by somatic cells within the developing gonads, we were able to highlight specific groups of genes expressed only in female or male germ cells. Our results provide an important resource for deciphering the molecular pathways driving proper germ cell development and sex determination and will improve our understanding of the etiology of human germ cell tumors that arise from dysregulation of germ cell differentiation.
| S-EPMC3062041 | biostudies-literature
Project description:Plants are dependent on divisions of stem cells to establish cell lineages required for growth. During embryogenesis, early division products are considered to be stem cells, whereas during post-embryonic development, stem cells are present in meristems at the root and shoot apex. PLETHORA/AINTEGUMENTA-LIKE (PLT/AIL) transcription factors are regulators of post-embryonic meristem function and are required to maintain stem cell pools. Despite the parallels between embryonic and post-embryonic stem cells, the role of PLTs during early embryogenesis has not been thoroughly investigated. Here, we demonstrate that the PLT regulome in the zygote, and apical and basal cells is in strong congruence with that of post-embryonic meristematic cells. We reveal that out of all six PLTs, only PLT2 and PLT4/BABY BOOM (BBM) are expressed in the zygote, and that these two factors are essential for progression of embryogenesis beyond the zygote stage and first divisions. Finally, we show that other PLTs can rescue plt2 bbm defects when expressed from the PLT2 and BBM promoters, establishing upstream regulation as a key factor in early embryogenesis. Our data indicate that generic PLT factors facilitate early embryo development in Arabidopsis by induction of meristematic potential.
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