Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to imidazolinone (Arsenal) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to primisulfuron (Beacon) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to sulfometuron methyl (oust XP) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to triazolopyrimidine (FirstRate) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesmRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting “mRNP code” determines the fate of any given mRNA and thus determines the gene regulation at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA binding factors characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3´UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently to their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability. Overall design: RNAseq experiments of HEK293 cells which were transfected with siRNAs targeting LARP4B and firefly luciferase as controls. The experiment was performed in triplicates.
LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.
No sample metadata fields
View SamplesGenome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, Time
View SamplesMaintenance and maturation of primordial germ cells is controlled by complex genetic and epigenetic cascades, and disturbances in this network lead to either infertility or malignant aberration. Transcription factor Tcfap2c / TFAP2C has been described to be essential for primordial germ cell maintenance and to be upregulated in several human germ cell cancers. Using global gene expression profiling, we identified genes deregulated upon loss of Tcfap2c in primordial germ cell-like cells. We show that loss of Tcfap2c affects many aspects of the genetic network regulating germ cell biology, such as downregulation maturation markers and induction of markers indicative of somatic differentiation, cell cycle, epigenetic remodeling, and pluripotency associated genes. Chromatin-immunoprecipitation analyses demonstrated binding of Tcfap2c to regulatory regions of deregulated genes (Sfrp1, Dmrt1, Nanos3, c-Kit, Cdk6, Cdkn1a, Fgf4, Klf4, Dnmt3b and Dnmt3l) suggesting that these genes are direct transcriptional targets of Tcfap2c in primordial germ cells. Since Tcfap2c deficient primordial germ cell like cells display cancer related deregulations in epigenetic remodeling, cell cycle and pluripotency control, the Tcfap2c-knockout allele was bred onto 129S2/Sv genetic background. There, mice heterozygous for Tcfap2c develop germ cell cancer with high incidence. Precursor lesions can be observed as early as E16.5 in developing testes displaying persisting expression of pluripotency markers. We further demonstrate, that mice with a heterozygous deletion of the Tcfap2c target gene Nanos3 are also prone to develop teratoma. These data highlight Tcfap2c as a critical and dose-sensitive regulator of germ cell fate.
Transcription factor TFAP2C regulates major programs required for murine fetal germ cell maintenance and haploinsufficiency predisposes to teratomas in male mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.
Specimen part, Time
View SamplesWhen macrophages encounter pathogens, they transiently induce an orchestrated cascade of pro- and anti-inflammatory genes. We systematically analyzed the contribution of translational regulation to the early phase of macrophage activation. While the expression of most cytokines is regulated by changes in mRNA levels, de-repression of translation was found to permit expression of many feedback inhibitors of the inflammatory response. This includes NF-kB inhibitors (IkBd, IkBz, Nr4a1, Ier3), a p38 MAPK antagonist (Dusp1) and post-transcriptional suppressors of cytokine expression (TTP and Zc3h12a). Ier3 is tightly co-regulated with TNF at the level of mRNA abundance and translation. Macrophages lacking Ier3 show reduced survival upon activation, indicating that induction of Ier3 is required to protect macrophages from lipopolysaccharide-induced cell death. Our analysis reveals an important role of translational regulation in the resolution of inflammation and macrophage survival.
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.
Specimen part
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