H3K27ac ChIP in Dicer KO/WT [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Sara Gosline
PROVIDER: E-GEOD-61034 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:RNA-Seq performed on Dicer KO and WT murine mesenchymal stem cells from total RNA MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression. Total RNA was analyzed from adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-), as well as from WT cells transfected with an empty vector or a vector containing Tead4, Sox9 or Pbx3 transcripts.
2015-12-15 | E-GEOD-61033 | biostudies-arrayexpress
Project description:RNA-Seq performed on Dicer KO and WT murine mesenchymal stem cells MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression. Examination of mature mRNA expression changes in adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-).
2014-11-17 | E-GEOD-61031 | biostudies-arrayexpress
Project description:RNA-Seq performed on Dicer KO and WT murine mesenchymal stem cells MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression.
2014-11-17 | GSE61031 | GEO
Project description:RNA-Seq performed on Dicer KO and WT murine mesenchymal stem cells from total RNA MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression.
2015-12-15 | GSE61033 | GEO
Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Examination of histone modifications in adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-).
2013-04-10 | E-GEOD-44159 | biostudies-arrayexpress
Project description:We performed ChIP-Seq of H3K27ac in duplicate in both WT and KO mesenchymal stem cells to evaluate global transcriptional changes between the new cells. We identified putative transcription factor binding sites using GEM v1.1 in K27ac data as well as in p MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression.
2015-12-15 | GSE61034 | GEO
Project description:MicroRNAs (miRNAs) are small, endogenous, non-protein coding RNAs that are an important means of post-transcriptional gene regulation. Deletion of Dicer, a key miRNA processing enzyme, is embryonic lethal in mice, and tissue-specific Dicer deletion results in developmental defects. Using a conditional knockout model, we generated mice lacking Dicer in the adrenal cortex. These Dicer knockout (KO) mice exhibited perinatal mortality and failure of the adrenal cortex during late gestation between embryonic day 16.5 (E16.5) and E18.5. Further study of Dicer KO adrenals demonstrated a significant loss of Sf1 expressing cortical cells that was histologically evident as early as E16.5 coincident with an increase in p21 and cleaved-caspase 3 staining in the cortex. However, peripheral cortical proliferation persisted in KO adrenals as assessed by anti-PCNA staining. To further characterize the embryonic adrenals from Dicer KO mice, we performed microarray analyses for both gene expression and miRNA on purified RNA isolated from control and KO adrenals of E15.5 and E16.5 embryos. Consistent with the absence of Dicer and the associated loss of miRNA-mediated mRNA degradation, we observed an up-regulation of a small subset of adrenal transcripts in Dicer KO mice, most notably the transcripts coded by the genes Nr6a1 and Acvr1c. Indeed, several miRNAs, including let-7, miR-34c, and miR-21 that are predicted to target these genes for degradation, were also markedly down-regulated in Dicer KO adrenals. Together these data suggest a role for miRNA mediated regulation of a subset of genes that are essential for normal adrenal growth and homeostasis. Adrenals from control and Dicer KO litter mates were pooled separately from 4 individual litters, resulting in a total of 4 control (cre-) and 4 Dicer KO biological
2013-05-01 | E-GEOD-45810 | biostudies-arrayexpress
Project description:DICER has a well-characterized role in the processing of microRNAs (miRNAs) and small interfering RNAs (siRNA) that are important for post-transcriptional gene regulation. Emerging evidence suggests that DICER also has several non-canonical functions beyond miRNA/siRNA biogenesis, for example in transcriptional gene silencing at the chromatin level, as well as in RNA degradation and maintenance of genomic integrity. We have shown that the function of DICER in germ cells is essential for normal spermatogenesis; male mice lacking DICER in postnatal male germ cells are infertile due to severe defects in haploid differentiation. To better understand the function of DICER in male germ cells, we immunoprecipitated DICER from juvenile mouse testes and performed mass spectrometric analysis to identify DICER-interacting proteins.
2020-06-03 | PXD017772 | Pride
Project description:We have used genome editing to generate inactivating deletion mutations in all three copies of the dicer (hdcr) gene present in the human cell line 293T. As previously shown in murine ES cells lacking Dicer function, hDcr-deficient 293T cells are severely impaired for the production of mature microRNAs (miRNAs). Nevertheless, RNA-induced silencing complexes (RISCs) present in these hDcr-deficient cells are readily programmed by transfected, synthetic miRNA duplexes to repress mRNAs bearing either fully or partially complementary targets, including targets bearing incomplete seed homology to the introduced miRNA. Using these hDcr-deficient 293T cells, we demonstrate that human pre-miRNA processing can be effectively rescued by ectopic expression of the Drosophila Dicer 1 protein, but only in the presence of the PB isoform of Loquacious (Loqs-PB), the fly homolog of the hDcr co-factor TRBP. In contrast, Drosophila Dicer 2, even in the presence of its co-factors Loqs-PD and R2D2, was unable to support human pre-miRNA processing. Interestingly, although ectopic Drosophila Dicer 1/Loqs-PB or hDcr both rescued pre-miRNA processing effectively in these hDcr-deficient cells, there were significant differences in the ratio of the miRNA isoforms that were produced, especially in the case of miR-30 family members, and we also noted differences in the relative expression level of miRNAs versus passenger strands for a subset of human miRNAs. These data demonstrate that the mechanisms underlying the accurate processing of pre-miRNAs are largely, but not entirely, conserved between mammalian and insect cells. Series includes three datasets of total small RNA reads from wild type and Dicer negative 293T cells. Also included are total small RNA reads of the Dicer-negative cell line NoDice(4-25) transfected with a vector expressing human Dicer, Drosophila Dicer1, or mock transfected. RISC-associated small RNAs identified by ribonucleoprotein immunoprecipitation (RIP-Seq) in wild type 293T, Dicer-negative NoDice(4-25) line, and NoDice(4-25) transfected with either hsa-miR-155 or kshv-miR-K12-11 miRNA duplexes. The final data series are PAR-CLIP libraries which identified microRNA targets in untransfected NoDice(4-25) cells and NoDice(4-25) cells transfected with either hsa-miR-92a, hsa-miR-155, kshv-miR-K12-11 miRNA duplexes
2014-04-17 | E-GEOD-56836 | biostudies-arrayexpress
Project description:Dicer is an essential ribonuclease involved in the biogenesis of miRNA. Previous studies have reported that Dicer is dysregulated in multiple types of cancers. To investigate the downstream phosphoproteome of Dicer, we carried out phosphotyrosine profiling of the liver of Dicer knockout of mice. We employed antibody-based enrichment of phosphotyrosine containing peptides coupled with spike-in SILAC-based quantitation. Over 400 phosphoisites were identified in each condition while 290 phosphosites were quantitated in common. Amongst these, several key signaling molecules like receptor tyrosine kinase MET, MET, PDGFR, EPHA2, EPHB4 and IGF1R/INSR were hyperphosphorylated. Also, non-receptor tyrosine kinases of Src family and their downstream effector signaling partners including IRS2 and STAT3were found to be hyperphosphorylated. Our study indicates that there is significant alteration in the signaling pathways upon ablation of Dicer.
2016-07-08 | PXD000927 | Pride