The nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Common genomic elements promote transcriptional and DNA replication roadblocks.
Subject
View SamplesSamples in this study probe the gene expression kinetics in human CCR6+ Th17 memory T cells activated under Th17 condition. Human CCR6+ Th17 memory T cells were purified from PBMC and gene expression was studied over a time course of 3 days after activation under Th17 condition. RNA from these samples was also profiled using RNA-Seq to compare different transcriptome profiling technologies.
Comparison of RNA-Seq and microarray in transcriptome profiling of activated T cells.
No sample metadata fields
View SamplesPurpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study was to obtain the trasncriptome of DGCR8_KO mESCs to compare it with the transcriptome of WT mESCs (deposit separately). Overall design: mRNA profiles of DGCR8_KO mouse embryonic stem cells were generated by deep sequencing, in duplicate, using Illumina HiSeq2000.
Noncanonical function of DGCR8 controls mESC exit from pluripotency.
Specimen part, Cell line, Subject
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View SamplesProper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for reproduction. We performed RNAseq of 3 maturaton staged gonadotrope cell lines, a thyroptrope cell line and NIH-3T3 cells to establish the timing and expression levels of genes involved in gonadotrope maturation. Overall design: Rna-seq of 3 mouse gonadotrope cell lines, 1 mouse thyrotrope cell line and NIH-3T3 cell line
Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.
Cell line, Subject
View SamplesAlthough it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it generally remains unclear whether the phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a known ligand-receptor interaction and thereby enable pharmacological interrogation of the specificity of the offspring response, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that chronic paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in the next generation. This effect manifested as increased survival following an injection of toxic levels of either nicotine or of cocaine, was specific to male offspring, and was only observed after offspring were first acclimated to sublethal doses of nicotine or cocaine. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, accompanied by hepatic upregulation of genes involved in xenobiotic metabolism. Surprisingly, this protective effect could also be induced by paternal exposure to a nicotinic receptor antagonist as well as to nicotine, suggesting that paternal xenobiotic exposure, rather than nicotinic receptor signaling, is likely to be responsible for programming of offspring drug resistance. Taken together, our data show that paternal drug exposure can induce a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment. Overall design: Hepatocytes were isolated from 8 week-old male F1 animals from control (TA) and nicotine-exposed (NIC) fathers, and allowed to adhere to the bottom of the well for three hours. Nonadherent cells were then removed, and fresh culture medium was then added. Cells were harvested at different time points in Trizol, and total RNA was extracted. Strand specific libraries were prepared from all samples, and sequenced on Illumina NextSeq500.
Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring.
Sex, Specimen part, Cell line, Subject
View SamplesWe performed microarray gene expression profiling in 16 T-ALL cell lines
Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesKaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). In sub-Saharan Africa, the high prevalence of both HIV-1 and KSHV has made KS a leading cancer in the region, associated with poor prognosis and high mortality due to late medical presentation and advanced disease stages. A better understanding of the cellular and viral transcriptome profiles during neoplastic growth will aid in the definition of biomarkers and cellular functions associated with KS tumorigenesis and progression. Our approach is to examine the transcriptome profile in actual KS lesions versus non-cancer tissues from the same individual for a total of four male African epidemic KS patients. These patients have undetectable HIV-1 plasma viral load after successful anti-retroviral therapy. Our results capture the cellular complexity of in vivo lesion environment and provide a marked contrast to those derived from in vitro monoculture models. The findings demonstrate that latency and immune modulation related functions dominate the viral gene expression pattern. Moreover, KSHV significantly affected the cellular transcriptome profile with genes involved in lipid and glucose metabolism disorder pathways being the most substantially dysregulated. Despite the implied infiltration of immune cells into the lesions as predicted by CIBERSORT, KS tumor continued to progress, suggesting immunological dysfunction in these KS patients despite control of HIV-1 viremia. Lastly, there is limited overlap of our in vivo dataset with in vitro studies, suggesting a limitation of in vitro KS models. Overall design: RNA-seq of Kaposi's sarcoma lesions and control tissues
RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.
Specimen part, Subject
View SamplesWe used microarrays to detail the global program of gene expression in cytokine stimulated effector CD8 T cells.
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Specimen part
View SamplesTo identify genes more highly expressed in Myeloma celllines v.s lymphoma cell lines.
IRF4 addiction in multiple myeloma.
Specimen part
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