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FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [nanostring]

ABSTRACT: FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [nanostring]

PROVIDER: PRJNA412400 | ENA |

REPOSITORIES: ENA

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FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes

Project description:FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes

| PRJNA412398 | ENA

FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [microarray]

Project description:FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [microarray]

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FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [nanostring]

Project description:Nanostring profiles of CD4+ T cells transduced with EV, WT or FoxP3 mutants

2017-09-28 | GSE104344 | GEO

FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes.

Project description:FoxP3+ regulatory T cells (Tregs) are a central element of immunological tolerance. FoxP3 is the key determining transcription factor of the Treg lineage, interacting with numerous cofactors and transcriptional targets to determine the many facets of Treg function. Its absence leads to devastating lymphoproliferation and autoimmunity in scurfy mutant mice and immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) patients. To finely map transcriptionally active regions of the protein, with respect to disease-causing variation, we performed a systematic alanine-scan mutagenesis of FoxP3, assessing mutational impacts on DNA binding and transcriptional activation or repression. The mutations affected transcriptional activation and repression in a variegated manner involving multiple regions of the protein and varying between different transcriptional targets of FoxP3. There appeared to be different modalities for target genes related to classic immunosuppressive function vs. those related to atypical or tissue-Treg functions. Relevance to in vivo Treg biology was established by introducing some of the subtle Foxp3 mutations into the mouse germline by CRISPR-based genome editing. The resulting mice showed Treg populations in normal numbers and exhibited no overt autoimmune manifestations. However, Treg functional defects were revealed upon competition or by system stress, manifest as a strikingly heightened susceptibility to provoked colitis, and conversely by greater resistance to tumors. These observations suggest that some of the missense mutations that segregate in human populations, but do not induce IPEX manifestations, may have unappreciated consequences in other diseases.

| S-EPMC5777076 | biostudies-literature

FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-09-28 | GSE104346 | GEO

FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [microarray]

Project description:Microarray profiles of M176, M354 and WT FoxP3 -transdued (in vitro) and -Treg from mice

2017-09-28 | GSE104345 | GEO

High-resolution mapping of HP1 redistribution in a position-effect variegation model

Project description:Position-effect variegation (PEV) is the stochastic transcriptional silencing of a gene positioned adjacent to heterochromatin. white-mottled X-chromosomal inversions in Drosophila are classic PEV models that show variegation of the eye color gene white due to its relocation next to pericentric heterochromatin. To obtain insight into the mechanism of PEV, we constructed detailed binding maps of Heterochromatin Protein 1 (HP1), a major component of heterochromatin, on white-mottled chromosomes. We find that HP1 invades euchromatin across the inversion breakpoints over ~175kb and ~30kb, causing de novo association of HP1 with 20 genes. However, HP1 binding levels in these regions show substantial local variation; white is most strongly bound by HP1 and is one of only two genes that are substantially repressed by heterochromatin. HP1 binding to the invaded region is exceptionally sensitive to the dosage of the histone methyltransferase Su(var)3-9, indicating that the de novo formed heterochromatin is relatively unstable. Our molecular maps demonstrate that heterochromatin can invade a normally euchromatic region, yet the strength of HP1 binding and effects on gene expression are highly dependent on local context. Keywords: DamID, gene expression, genetic modification.

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Atypical porcine pestivirus

Project description:Atypical porcine pestivirus Genome sequencing

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The ASC-1 complex promotes translation initiation of the scanning ribosomes

Project description:Translation is initiated by binding of the eIF4F complex to the 5' cap of the mRNA, which is followed by scanning of the initiation codon by scanning ribosomes. Here we demonstrate that the ASC-1 complex (ASCC), which was previously shown to promote the dissociation of colliding 80S ribosomes, associates with the scanning ribosomes to regulate translation initiation. Sel-TCP-seq analysis revealed that ASCC3, a subunit of ASCC with a helicase domain, localizes predominantly to the 5' untranslated region of mRNAs. Knockdown of ASCC3 resulted in reduced translation efficiency associated with reduced 43S preinitiation complex (PIC) loading and a reduced speed of scanning ribosomes. In addition, depletion of the ubiquitin ligase ZNF598, a sensor of collided 80S ribosomes, also reduces the PIC loading and speed of scanning ribosomes. Our results have thus revealed that ASCC is required not only for dissociation of colliding 80S ribosomes, but also for efficient translation initiation by scanning ribosomes.

2023-03-31 | GSE186502 | GEO

Ion AmpliSeq transcriptome analysis of atypical hepatocytes

Project description:We compared transcriptome between atypical and non-atypical hepatocytes by RNA-seq

2020-07-03 | GSE153742 | GEO