This SuperSeries is composed of the SubSeries listed below.
HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy.
Cell line, Treatment
View SamplesWe compared in triplicate mRNA levels from cells treated with siRNA against either HCF-1 or, as a negative control, luciferase. We observed that 19% of Refseq annotated genes are differentially expressed (either up or down regulated with a multiple testing corrected p value of 0.05) upon depletion of HCF-1. This large number of differentially expressed genes upon HCF-1 depletion demonstrates a broad role of HCF-1 in the regulation of gene expression.
HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Specimen part
View SamplesMicroRNAs (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. Overall design: mRNAs from adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-), were analyzed. WT and KO cells were transfected with a nontargeting control siRNA. KO cells were separately transfected with a synthetic let-7g siRNA duplex, or an siRNA targeting Nr6a1.
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Specimen part, Cell line, Subject
View SamplesMicroRNAs (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.
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Specimen part
View SamplesMicroRNAs (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. Overall design: mRNAs from Flag-HA-NR6A1-overexpressing Dicer wild-type adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) and vector-only Dicer WT MSCs were analyzed.
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Specimen part, Cell line, Subject
View SamplesMicroRNAs (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. Overall design: Small RNAs from adult mesenchymal stem cells (immortalized clonal lines of murine MSCs) with and without Dicer (Dicer f/f, Dicer -/-) were analyzed.
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Specimen part, Cell line
View SamplesRNA-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. Overall design: 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.
Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements.
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