Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3 untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice.
Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation.
Specimen part
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
View SamplesIn fission yeast, the nuclear-localized Lsk1p-Lsc1p-Lsg1p cyclin dependent kinase complex is required for the reliable execution of cytokinesis and is also required for Ser-2 phosphorylation RNA pol II carboxy terminal domain.
Global gene expression analysis of fission yeast mutants impaired in Ser-2 phosphorylation of the RNA pol II carboxy terminal domain.
No sample metadata fields
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesWhile histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes. Overall design: Human aortic endothelial cells from a diabetic and non-diabetic individual were stimulated with DMSO (control), SAHA (2 µM, HDAC inhibitor) or C646 (10 µM, EP300 inhibitor) for 12 hours, or EP300 siRNA or non-target siRNA (control) for 4 hours, followed by 48 hours in fresh media. Study performed in triplicate.
Systems approach to the pharmacological actions of HDAC inhibitors reveals EP300 activities and convergent mechanisms of regulation in diabetes.
No sample metadata fields
View SamplesAlveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Comparative transcriptome analysis of equine alveolar macrophages.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View SamplesMammalian insulin and IGF induce similar but not identical changes in gene expression downstream of their respective receptors. Signaling bias at the receptor differentiates the two similar ligands, though the precise mechanism is not entirely understood. We used Drosophila insulin-like peptides DILP2 and DILP5 to determine how similar insulin-like ligands regulate similar and distinct patterns of gene expression in S2 cells by RNA-Seq. Overall, DILP2 and DILP5 stimulate many of the same changes in gene expression. However, some genes are uniquely regulated by DILP2 or by DILP5. Shared and distinct gene targets were validated by q-RT-PCR with indepedent replicates. Some unique gene targets of DILP2 are involved in sugar metabolism, which is functionally related in vivo to DILP2 and not DILP5. We find that gene expression is largely regulated in parallel by DILP2 and DILP5 but some key unique targets may lead to differential physiological functions for the two insulin-like genes. Overall design: mRNA profiles from S2 cells treated with DILP2, DILP5 or solvent were sequenced on an Illumina HiSeq2500
<i>Drosophila</i> Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity.
Cell line, Treatment, Subject
View SamplesMicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We now demonstrate that endogenous and over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). We report that the seed region of moR-21 as well as the seed match region in the target gene 3'UTR are indispensable for moR-21-mediated gene down-regulation. We further demonstrated that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. Taken together, these findings provide the first evidence that microRNA offset RNA regulates gene expression and is biologically active.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View Samples