*MMP1* bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms
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ABSTRACT:
PROVIDER: PRJNA131673 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE23068: Gene expression profiling of HUVEC under basal (resting) conditions GSE23069: Gene expression profiling of HUVEC after stimulation with an inflammatory mediator cocktail Refer to individual Series
2011-07-19 | E-GEOD-23070 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-07-20 | GSE23070 | GEO
Project description:Identifying the functional importance of the millions of single nucleotide polymorphisms (SNPs) in the human genome is a difficult challenge. Therefore, a reverse strategy, which identifies functionally important SNPs by virtue of the bimodal abundance across the human population of the SNP-related mRNAs will be useful. Those mRNA transcripts that are expressed at two distinct abundances in proportion to SNP allele frequency may warrant further study. Matrix metalloproteinase 1 (MMP1) is important in both normal development and in numerous pathologies. Although much research has been conducted to investigate the expression of MMP1 in many different cell types and conditions, the regulation of its expression is still not fully understood.In this study, we used a novel but straightforward method based on agglomerative hierarchical clustering to identify bimodally expressed transcripts in human umbilical vein endothelial cell (HUVEC) microarray data from 15 individuals. We found that MMP1 mRNA abundance was bimodally distributed in un-treated HUVECs and showed a bimodal response to inflammatory mediator treatment. RT-PCR and MMP1 activity assays confirmed the bimodal regulation and DNA sequencing of 69 individuals identified an MMP1 gene promoter polymorphism that segregated precisely with the MMP1 bimodal expression. Chromatin immunoprecipitation (ChIP) experiments indicated that the transcription factors (TFs) ETS1, ETS2 and GATA3, bind to the MMP1 promoter in the region of this polymorphism and may contribute to the bimodal expression.We describe a simple method to identify putative bimodally expressed RNAs from transcriptome data that is effective yet easy for non-statisticians to understand and use. This method identified bimodal endothelial cell expression of MMP1, which appears to be biologically significant with implications for inflammatory disease. (271 Words).
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Project description:Phenotype of Mrps5-associated polymorphisms is intimately linked to mitoribosomal misreading
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Project description:Gene expression can be highly heterogeneous in clonal cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states, and consequently a population will be composed of cells that are ‘ON’ and cells that are ‘OFF’. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessary source of heterogeneity that must be amplified by autostimulatory feedback regulation to obtain the bimodal response. A classical model of bistable differentiation is the development of genetic competence in Bacillus subtilis. Noise in expression of the transcription factor ComK ultimately determines the fraction of cells that enter the competent state. Due to its intrinsic random nature, noise is difficult to investigate. We adapted an artificial autostimulatory loop that bypasses all known ComK regulators, to screen for possible factors that affect noise in the bimodal regulation of ComK. This led to the discovery of Kre, a novel factor that controls the bimodal expression of ComK. Kre appears to affect the stability of comK mRNA. Interestingly, ComK itself represses the expression of kre, adding a new double negative feedback loop to the intricate ComK regulation circuit. Our data emphasize that mRNA stability is an important factor in bimodal regulation.
2017-02-10 | GSE61757 | GEO
Project description:Specific genes or encoded proteins are involved in regulating various learning models of different species through certain signaling pathways，but whether there are also regulatory genes during bimodal learning and memory is largely unknown. Using a multi-omics approach to examine gene expression changes in bees brain performed with three different learning assays, a general up-regulation of genes and proteins were observed in bimodal learning compared to controls. Protein-protein network predictions of differential proteins together with FISH assays suggest ALDH7A1 may be involved in regulation of bimodal learning and memory. Injecting siRNA-ALDH7A1 to the bee brain results in significant inhibition the expressions of ALDH7A1 and regucalcin, and increase β-alanine content. Interestingly, we found that loss of ALDH7A1 only affect visual-olfactory bimodal learning and memory, but not single visual or olfactory conditioned learning after ALDH7A1-RNAi in bees. Therefore, our data suggests that ALDH7A1 may affect bimodal learning and memory though controlling β-alanine related plasticity mechanisms.
2021-09-13 | PXD017008 | Pride
Project description:To cope with sudden changes in their environment, bacteria can use a bet-hedging strategy by dividing the population into cells with different properties. This so called bimodal or bistable cellular differentiation is generally controlled by positive feedback regulation of transcriptional activators. Due to continued turnover of the cytoplasmic content, it is difficult for these activators to reach an activation threshold concentration when cells are growing exponentially. This is one reason why bimodal differentiation is primarily observed from the onset of the stationary phase when exponential growth ceases. An exception is the bimodal induction of motility in Bacillus subtilis, which occurs early during exponential growth. Several mechanisms have been put forward to explain this, including double negative-feedback regulation and the stability of the mRNA molecules involved. In this study, we used fluorescence-assisted cell sorting to compare the transcriptome of motile and non-motile cells and noted that expression of ribosomal genes is lower in motile cells. This was confirmed using an unstable GFP reporter fused to the strong ribosomal rpsD promoter. We propose that the reduction in ribosomal gene expression in motile cells is the result of a diversion of cellular resources to the synthesis of the chemotaxis and motility systems. In agreement, single-cell microscopic analysis indicates that motile cells are slightly shorter than non-motile cells, an indication of slower growth. We speculate that this growth rate reduction can contribute to the bimodal induction of motility during exponential growth.
2021-01-20 | GSE164348 | GEO
Project description:To identify mediators of obesity-linked reductions in PGC-1, we tested the effects of cellular nutrients in C2C12 myotubes. While overnight exposure to high insulin, glucose, glucosamine, or amino acids had no effect, saturated fatty acids (FA) potently reduced PGC-1a and b mRNA expression. Experiment Overall Design: Cell culture - Mouse C2C12 myoblasts (ATCC, Manassas, VA) were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% fetal bovine serum (Invitrogen), at a confluency of 60-70%. To initiate differentiation, cells were allowed to reach 100% confluency and medium was changed to DMEM containing 2% horse serum (Invitrogen) and changed every 2 days. Full differentiation, with myotube fusion and spontaneous twitching, was observed at 5 days. Fatty acid stock preparation - Fatty acids were dissolved in 0.1 N sodium hydroxide (final concentration 100 mM) at 65 degrees C for 2 hours and then complexed with 10% fatty acid-free BSA, yielding a final stock of 5 mM. Three replicates for each fatty-acid. Microarray analysis - RNA was isolated as described from C2C12 myotubes treated overnight with 500 uM palmitate or 1% BSA, and cRNA was synthesized. 10 mg of cRNA were hybridized to Affymetrix mouse 430A 2.0 arrays. Intensity values were quantified using MAS 5.0 software. MAPPFinder (www.genmapp.org) was used to integrate expression data with known pathways. Transcription profiling of mouse C2C12 myotubes treated overnight with 500 uM palmitate or 1% BSA to identify mediators of obesity-linked reductions in PGC-1.
2007-11-15 | E-GEOD-6766 | biostudies-arrayexpress
Project description:We report a new technology for the parallel bimodal analysis of RNA-seq and ATAC-seq within a single-cell, known as ASTAR (Assay for Single-cell Transcriptome and Accessibility Regions).
2020-06-10 | GSE151734 | GEO
Project description:We report a new technology for the parallel bimodal analysis of RNA-seq and ATAC-seq within a single-cell, known as ASTAR (Assay for Single-cell Transcriptome and Accessibility Regions).
2020-06-10 | GSE151735 | GEO