This SuperSeries is composed of the SubSeries listed below.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View SamplesMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View SamplesMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Specimen part
View SamplesMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
No sample metadata fields
View SamplesEukaryotic mRNAs undergo a cycle of transcription, nuclear export, and degradation. A major challenge is to obtain a global, quantitative view of these processes. Here we measured the genome-wide nucleocytoplasmic dynamics of mRNA in Drosophila cells by metabolic labeling in combination with cellular fractionation. By mathematical modeling of these data we determined rates of transcription, export and cytoplasmic decay for >5,000 genes. We characterized these kinetic rates and investigated links with mRNA features, RNA-binding proteins (RBPs) and chromatin states. We found prominent correlations between mRNA decay rate and transcript size, while nuclear export rates are linked to the size of the 3''UTR. Transcription, export and decay rates are each associated with distinct spectra of RBPs. Specific classes of genes, such as those encoding cytoplasmic ribosomal proteins, exhibit characteristic combinations of rate constants, suggesting modular control. Overall, transcription and decay rates have a major impact on transcript abundance, while nuclear export is of minor importance. Finally, correlations between rate constants suggest global coordination between the three processes. Our approach should be generally applicable to other cell systems and provides insights into the genome-wide nucleocytoplasmic kinetics of mRNA. Overall design: 24 RNA-seq experiments comprising 2 biological replicates: pre-exsiting nuclear mRNA time 0h (samples 1&13), pre-exsiting nuclear mRNA time 0.5h (samples 2&14), pre-exsiting nuclear mRNA time 1.5h (samples 3&15) , pre-exsiting nuclear mRNA time 3h (samples 4&16), pre-exsiting nuclear mRNA time 5h (samples 5&17), pre-exsiting nuclear mRNA time 7.5h (samples 6&18), pre-exsiting cytoplasmic mRNA time 0h (samples 7&19), pre-exsiting cytoplasmic mRNA time 0.5h (samples 8&20), pre-exsiting cytoplasmic mRNA time 1.5h (samples 9&21) , pre-exsiting cytoplasmic mRNA time 3h (samples 10&22), pre-exsiting cytoplasmic mRNA time 5h (samples 11&23), pre-exsiting cytoplasmic mRNA time 7.5h (samples 12&24)
Comprehensive analysis of nucleocytoplasmic dynamics of mRNA in Drosophila cells.
Cell line, Treatment, Subject
View SamplesIn mammals, the nuclear lamina interacts with hundreds of large genomic regions, termed lamina-associated domains (LADs) that are generally in a transcriptionally repressed state. Lamins form the major structural component of the lamina and have been reported to bind DNA and chromatin. Here we systematically evaluated whether lamins are necessary for the peripheral localization of LADs in murine embryonic stem cells. Surprisingly, removal of essentially all lamins did not have any detectable effect on the genome-wide interaction pattern of chromatin with the inner nuclear membrane. This suggests that other components of the inner nuclear membrane mediate these interactions. Overall design: 2 samples, each with a biological replicate: wt mESC, B type lamin null (dKO) dKO mESC
Nuclear lamins are not required for lamina-associated domain organization in mouse embryonic stem cells.
No sample metadata fields
View SamplesAnalysis of the role of PARP1 in gene transcription in MCF7 cells under non-stress conditions. The hypothesis was that PARP1 activity in MCF7 cells plays a role in gene transcription. The results indicate that PARP1 inhibition does not significantly affect transcription after 6 hours of treatment.
Basal activity of a PARP1-NuA4 complex varies dramatically across cancer cell lines.
Specimen part, Cell line
View SamplesAnalysis of the role of PARP1 in gene transcription in cell lines with variable PARP1 activity.
Basal activity of a PARP1-NuA4 complex varies dramatically across cancer cell lines.
Specimen part, Cell line
View SamplesA single replicate of exponentially growing DT40 CL18 chicken B lymphoma cells were harvested and extracted RNA was subjected to Illumina GAIIx paired-end sequencing to determine global gene expression. Overall design: Single replicate RNA-seq expression analysis of DT40 cells.
Third Report on Chicken Genes and Chromosomes 2015.
Specimen part, Cell line, Subject
View SamplesThe aim of this experiment is to determine the similarities and differences between gene expression profiles in HepaRG cells versus primary human hepatocytes, human liver, and the commonly used HepG2 cell.
A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues.
Sex, Specimen part, Cell line
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