Rsf1p is a putative transcription factor required for efficient growth using glycerol as sole carbon source but not for growth on the alternative respiratory carbon source ethanol.
Rsf1p is required for an efficient metabolic shift from fermentative to glycerol-based respiratory growth in S. cerevisiae.
No sample metadata fields
View SamplesPDX tumors at various passages post first implantation in nude mice
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.
No sample metadata fields
View SamplesIt is fundamentally unknown how normal cellular processes or responses to extracellular stimuli may invoke polyadenylation and degradation of ncRNA substrates or if human disease processes exhibit defects in polyadenylation of ncRNA substrates as part of their pathogenesis. Our results demonstrate that mononuclear cells from subjects with relapsing-remitting multiple sclerosis (RRMS) exhibit pervasive increases in levels of polyadenylated ncRNAs including Y1 RNA, 18S and 28S rRNA, and U1, U2, and U4 snRNAs and these defects are unique to RRMS. Defects in expression of both Ro60 and La proteins in RRMS appear to contribute to increased polyadenylation of ncRNAs. Further, IFN-ß1b, a common RRMS therapy, restores both Ro60 and La levels to normal as well as levels of polyadenylated Y1 RNA and U1 snRNA suggesting that aberrant polyadenylation of ncRNA substrates may have pathogenic consequences. Overall design: We extracted RNA from peripheral whole blood in healthy control subjects and patients with established relapsing-remitting multiple sclerosis using PaxGene tubes.
Defective structural RNA processing in relapsing-remitting multiple sclerosis.
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View SamplesTo improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions. The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes. These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies. Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs. Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes. Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13. Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Overall design: Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.
Expression and functions of long noncoding RNAs during human T helper cell differentiation.
No sample metadata fields
View SamplesWe used Affymetrix DNA arrays to investigate the extent to which nuclear HDAC4 accumulation affects neuronal gene expression.
HDAC4 governs a transcriptional program essential for synaptic plasticity and memory.
Specimen part
View SamplesThe Carboxy-terminal domain (CTD) of RNA Polymerase II (RNAPII) in mammals undergoes extensive post-translational modification, which is essential for transcriptional initiation and elongation. Here, we show that the CTD of RNAPII is methylated at a single arginine (R1810) by the transcriptional co-activator CARM1. Although methylation at R1810 is present on the hyper-phosphorylated form of RNAPII in vivo, Ser-2 or Ser-5 phosphorylation inhibit CARM1 activity towards this site in vitro, suggesting that methylation occurs before transcription initiation. Mutation of R1810 results in the mis-expression of a variety of snRNAs and snoRNAs, an effect that is also observed in Carm1-/- MEFs. These results demonstrate that CTD methylation facilitates the expression of select RNAs, perhaps serving to discriminate the RNAPII-associated machinery recruited to distinct gene types. Overall design: To address the function of RNAPII methylation, we generated Raji cell lines expressing an RNA Polymerase II resistant to a-amanitin and carrying either wild-type R1810 or an arginine to alanine substitution at that same residue, abolishing R1810 methylation of the CTD. In cells cultured in a-amanitin, the a-amanitin-resistant mutants fully replaced the functions of endogenous RNAPII, allowing us to study if gene-expression is affected by the absence of R1810me
The C-terminal domain of RNA polymerase II is modified by site-specific methylation.
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View SamplesThis study sought to evaluate the effects of dietary MeHg exposure on adult female yellow perch (Perca flavescens) and zebrafish (Danio rerio) reproduction by relating controlled exposures with subsequent reproductive effects. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg. MeHg exposures at environmentally relevant levels were done in zebrafish for a full life cycle, mimicking a realistic exposure scenario, and in adult yellow perch for twenty weeks, capturing early seasonal ovarian development. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-seq and QPCR, but no significant phenotypic or physiological changes were observed with ovarian staging, fecundity, or embryo mortality. Yellow perch did not appear to be affected by MeHg, either at a molecular level, as assessed by QPCR of eight genes in the pituitary, liver, and ovary tissue, or a physiological level, as seen with ovarian somatic index, circulating estradiol, and ovarian staging. Lack of impact in yellow perch limits the usefulness of zebrafish as a model and suggests that the reproductive sensitivity to environmentally relevant levels of MeHg differs between yellow perch and zebrafish. Overall design: 12 samples of total RNA isolated from adult zebrafish ovaries were analyzed. Each exposure group (1, 3, and 10 ppm MeHg) had three replicates, as did the vehicle control. Each sample was comprised of pooled total RNA of up to 6 individual fish.
Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio).
No sample metadata fields
View SamplesGene expression profiling is an important tool in the development of medical countermeasures against chemical warfare agents (CWAs). Non-human primates (NHPs), specifically the rhesus macaque (Macaca mulatta), the cynomologus macaque (Macaca fascicularis) and the African green monkey (Chlorocebus aethiops), are vital models in the development of CWA prophylactics, therapeutics, and diagnostics. However, gene expression profiling of these NHPs is complicated by the fact their genomes are not completely sequenced, and that no commercially available oligonucleotide microarrays (genechips) exist. We, therefore, sought to determine whether gene expression profiling of NHPs could be performed using human genechips. Whole blood RNA was isolated from each species and used to generate genechip probes. Hybridization of the NHP samples to human genechips (Affymetrix Human U133 Plus 2.0) resulted in comparable numbers of transcripts detected compared with human samples. Statistical analysis revealed intraspecies reproducibility of genechip quality control metrics; interspecies comparison between NHPs and humans showed little significant difference in the quality and reproducibility of data generated using human genechips. Expression profiles of each species were compared using principal component analysis (PCA) and hierarchical clustering to determine the similarity of the expression profiles within and across the species. The cynomologus group showed the least intraspecies variability, while the human group showed the greatest intraspecies variability. Intraspecies comparison of the expression profiles identified probesets that were reproducibly detected within each species. Each NHP species was found to be dissimilar to humans; the cynomologus group was the most dissimilar. Interspecies comparison of the expression profiles revealed probesets that were reproducibly detected in all species examined. These results show that human genechips can be used for expression profiling of NHP samples and provide a foundation for the development of tools for comparing human and NHP gene expression profiles.
Comparison of non-human primate and human whole blood tissue gene expression profiles.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Age, Specimen part
View SamplesBisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure toBPAin utero hasbeen linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen related disease in adults.Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Age, Specimen part
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