The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes. Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasites advantage.
Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite.
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View SamplesZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA. Likewise, knockdown of ZXDC1 restricts the induced expression of these markers. We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Specimen part, Cell line
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Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part, Cell line
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesFoxO6 is expressed in the brain, craniofacial region and somite, but the precise role of FoxO6 in craniofacial development remain unknown. We found that FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull.
FoxO6 regulates Hippo signaling and growth of the craniofacial complex.
Specimen part
View SamplesHuman genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3'' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from RNA-seq experiments. Overall design: We performed RNA-seq to profile gene expression and splicing changes. The expression levels of Rbfox1 and Rbfox3 in cultured mouse hippocampal neurons were reduced by siRNAs. The reduction of Rbfox1 and 3 was rescued by expression of cytoplasmic or nuclear Rbfox1 splice isoform. The gene expression and splicing profiles were compared between different treatments. Eight samples were analyzed.
Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes.
No sample metadata fields
View SamplesRegulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
No sample metadata fields
View SamplesThis study was aimed at elucidating the mechanisms underlying activity-dependent gene regulation during LTP of mouse hippocampal CA3-CA1 synapses. Deep sequencing of the 3' end of transcripts allowed to identify changes in APA induced 1 hour and 3 hours after LTP induction. We detected APA changes that only affected the 3''UTR (3''UTR-APA events) and APA changes that also affected the coding sequence (CDS-APA events). Overall design: We performed 3' region extraction and deep sequencing (3''READS) of acute hippocampal slices 1 hour and 3 hours after LTP induction, and of time-matched control slices. Hippocampal slices were prepared from 2-3 month old C57BL/6 wild-type mice, the dentate gyrus was trimmed, and the slices were placed in interface chambers to recover for 2 hours with continuous ACSF perfusion. From the same animal, half of the mini-slices were used for LTP induction (using a pharmacological protocol, cLTP) and the remaining slices were treated with a DMSO vehicle solution as controls. We sequenced triplicates (samples 1-3) of controls and cLTP treated slices for the 1 hour and 3 hours time-point.
Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.
Age, Specimen part, Cell line, Subject
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