The endogenous retrovirus Mtv8 which resides within the V kappa locus does not influence the mouse immunoglobulin repertoire
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ABSTRACT:
PROVIDER: PRJNA1043706 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26906012_1.fastq.gz | Fastqsanger.gz | |||
| SRR26906012_2.fastq.gz | Fastqsanger.gz | |||
| SRR26906013_1.fastq.gz | Fastqsanger.gz | |||
| SRR26906013_2.fastq.gz | Fastqsanger.gz | |||
| SRR26906014_1.fastq.gz | Fastqsanger.gz |
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Project description:The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number of pathogens. The antigen receptor repertoire is built during the recombination and hypermutation of B and T cell receptor (B-, TCR) loci. V(D)J recombination rearranges these antigen receptor loci which are organized as an array of separate V, (D), and J gene segments. Which gene segments are recombined, and thus which particular antigen receptors are present in the host repertoire, depends on the three-dimensional architecture of the recombining locus. The endogenous retrovirus (ERV) mouse mammary tumor provirus (Mtv8) resides on mouse chromosome 6 interposed within the large array of light chain kappa (IgK) V gene segments. It was unknown, however, whether Mtv8 influences the BCR repertoire, as ERVs can contribute to changes in genomic architecture by driving high levels of local transcription. We generated Mtv8-deficient mice to determine if the ERV influenced V(D)J recombination and found no significant difference in the peripheral BCR repertoire of Mtv8-deficient mice compared to wildtype controls. Thus, Mtv8, the endogenous retrovirus in the Igk locus, does not influence BCR repertoires.
2023-11-27 | GSE248410 | GEO
Project description:Background: V(D)J recombination is an essential process for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igk) light chain locus recombination follows recombination of the immunoglobulin heavy chain (Igh) locus. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. In conjunction with genome-wide datasets for several epigenetic features, we showed that two active chromatin states, located at the recombination signal sequences (RSS) of VH genes, are highly predictive of recombination. The contribution of chromatin features to Vk gene choice in recombination remains poorly understood. Results: We adapted the VDJ-seq assay to profile the Igk VkJk repertoire, and obtained a comprehensive readout of highly variable Vk gene usage in mouse bone marrow pre-B cells. We identified PU.1 binding at the RSS as highly predictive of whether a gene will actively recombine or not. Prediction of the frequency of recombination was more dependent on H3K4 methylation and IKAROS binding. Conclusions: Epigenetic features within the Vk region are able to explain much of the variation in Vk gene usage. Whilst PU.1 binding at the RSS appears to play a binary, all-or-nothing role, priming Vk genes for recombination, the frequency with which these genes recombine is shaped by the presence and enrichment of a number of other epigenetic features. In contrast to the Igh locus, the epigenetic landscape of the promoter as well as the RSS is predictive of Vk gene recombination.
2017-11-03 | GSE101606 | GEO
Project description:Immunoglobulin Repertoire Analysis in PGNMID
| PRJEB88838 | ENA
Project description:The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins. we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins.
2025-06-04 | PXD061852 | Pride
Project description:Autoreactive B cells expressing two different immunoglobulin light chains are present in elevated numbers in a subset of systemic lupus erythematosus patients and in MRL and MRL/lpr mouse models of lupus. Using RNAseq and genetic pathway analyses together with in vitro studies we demonstrate a role for TLR and IFN signaling in MRL/lpr dual-κ B cell expansion and/or activation. Dual-κ cells also showed increased expression of co-receptors used for T cell cognate interaction as well as enrichment of pathways involved in their signaling. Overall, our studies identify molecular pathways involved in the enrichment of dual-reactive effector B cells and reveal potential targets for their selective ablation in autoimmunity.
2019-05-20 | GSE109147 | GEO
Project description:The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number of pathogens. The antigen receptor repertoire is built during the recombination of B and T cell receptor (BCR, TCR) loci and hypermutation of BCR loci. V(D)J recombination rearranges these antigen receptor loci, which are organized as an array of separate V, (D), and J gene segments. Transcription activation at the recombining locus leads to changes in the local three-dimensional architecture, which subsequently contributes to which gene segments are utilized for recombination. The endogenous retrovirus (ERV) mouse mammary tumor provirus 8 (Mtv8) resides on mouse chromosome 6 interposed within the large array of light chain kappa V gene segments. As ERVs contribute to changes in genomic architecture by driving high levels of transcription of neighboring genes, it was suggested that Mtv8 could influence the BCR repertoire. We generated Mtv8-deficient mice to determine if the ERV influences V(D)J recombination to test this possibility. We find that Mtv8 does not influence the BCR repertoire.
| S-EPMC10948529 | biostudies-literature
Project description:Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire
| PRJNA590489 | ENA
Project description:Productive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa (κ) or lambda (λ) light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the κ 3′ and λ enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the κ intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells. We used microarrys to identify the changes in gene expression under different levels of the cytokine IL-7 and after rescue of genetic defect. Keywords: growth conditions and rescue
2008-01-26 | GSE10273 | GEO
Project description:Cryptic endogenous retrovirus subfamilies in the primate lineage
| PRJNA1029531 | ENA
Project description:Using doxycycline-inducible IFN-kappa expression in CIN612-9E cells, which maintain extrachromosomally replicating HPV31 genomes, we demonstrate that IFN-kappa inhibits the growth of these cells and reduces viral transcription and replication. Interestingly, the initiation of viral early transcription was already inhibited 4-6h after IFN-kappa expression. This was also observed with recombinant IFN-beta suggesting a common mechanism of IFNs. RNA-seq analysis identified 1367 IFN-kappa regulated genes of which 221 were modulated >2-fold. The majority of those (71%) matched known ISGs confirming that IFN-kappa acts as a bona fide type I IFN in hr-HPV-positive keratinocytes. RNAi and co-transfection experiments indicate that the inhibition of viral transcription is mainly due to the induction of Sp100 proteins by IFN-kappa. CIN612-9E/pInd-IFN-kappa were induced for 4h with 1µg/ml doxycyclin or not. Three biological replicates were analyzed.
2015-11-04 | E-GEOD-74658 | biostudies-arrayexpress