Mus musculus strain:C57BL/6
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA226025 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1531330.fastq.gz | Fastqsanger.gz | |||
| SRR1531340.fastq.gz | Fastqsanger.gz | |||
| SRR1531350.fastq.gz | Fastqsanger.gz | |||
| SRR1531331.fastq.gz | Fastqsanger.gz | |||
| SRR1531341.fastq.gz | Fastqsanger.gz |
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Project description:During B cell development the precursor B cell receptor (pre-BCR) checkpoint is thought to increase immunoglobulin k light chain (Igk) locus accessibility to the V(D)J recombinase. Accordingly, pre-B cells lacking the pre-BCR signaling molecules Btk or Slp65 showed reduced germline Vk transcription. To investigate whether pre-BCR signaling modulates Vk accessibility through enhancer-mediated Igk locus topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B cells the k enhancers robustly interact with the ~3.2 Mb Vk region and its flanking sequences. Analyses in wild-type, Btk and Slp65 single and double-deficient pre-B cells demonstrated that pre-BCR signaling reduces interactions of both enhancers with Igk locus flanking sequences and increases interactions of the 3â??k enhancer with Vk genes. Remarkably, pre-BCR signaling does not significantly affect interactions between the intronic enhancer and Vk genes, which are already robust in pro-B cells. Both enhancers interact most frequently with highly used Vk genes, which are often marked by transcription factor E2a. We conclude that the k enhancers interact with the Vk region already in pro-B cells and that pre-BCR signaling induces accessibility through a functional redistribution of long-range chromatin interactions within the Vk region, whereby the two enhancers play distinct roles. We performed genome-wide expression profiling of FACS-purified B220+CD19+ pre-B cell fractions from wild-type (WT), Btk and Slp65 single and double deficient VH81x transgenic Rag1-/- mice (n=4 of each genotype). In these experiments non-VH81x transgenic Rag1-/- pro-B cells served as controls (n=3).
2014-03-21 | E-GEOD-53896 | biostudies-arrayexpress
Project description:During B cell development the precursor B cell receptor (pre-BCR) checkpoint is thought to increase immunoglobulin k light chain (Igk) locus accessibility to the V(D)J recombinase. Accordingly, pre-B cells lacking the pre-BCR signaling molecules Btk or Slp65 showed reduced germline Vk transcription. To investigate whether pre-BCR signaling modulates Vk accessibility through enhancer-mediated Igk locus topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B cells the k enhancers robustly interact with the ~3.2 Mb Vk region and its flanking sequences. Analyses in wild-type, Btk and Slp65 single and double-deficient pre-B cells demonstrated that pre-BCR signaling reduces interactions of both enhancers with Igk locus flanking sequences and increases interactions of the 3’k enhancer with Vk genes. Remarkably, pre-BCR signaling does not significantly affect interactions between the intronic enhancer and Vk genes, which are already robust in pro-B cells. Both enhancers interact most frequently with highly used Vk genes, which are often marked by transcription factor E2a. We conclude that the k enhancers interact with the Vk region already in pro-B cells and that pre-BCR signaling induces accessibility through a functional redistribution of long-range chromatin interactions within the Vk region, whereby the two enhancers play distinct roles.
2014-03-21 | GSE53896 | GEO
Project description:Pre-BCR Signaling induce IgK Locus Accessibility by functional redistribution of Enhancer-mediated chromatin Interactions
2015-07-31 | E-GEOD-53896 | ExpressionAtlas
Project description:Pre-BCR Signaling induce IgK Locus Accessibility by functional redistribution of Enhancer-mediated chromatin Interactions
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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 3Ⲡand 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. Experiment Overall Design: IRF4,8 null pre-B cells were cultures in the indicated conditions prior to RNA isolation and hybridization to Affymetrix arrays.
2008-06-11 | E-GEOD-10273 | biostudies-arrayexpress
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:Antigen receptor loci are organized into variable (V), diversity (D), and joining (J) elements that rearrange to generate diverse antigen receptor repertoires. Here, we identified an enhancer (E34) in the immunoglobulin kappa locus (Igκ) that instructed rearrangement of Vκ genes located in a sub-topologically associating domain (subTAD), including a Vκ gene encoding for antibodies targeting bacterial phosphorylcholine. E34 promoted the deposition of active histone marks across the E34 subTAD to instruct its nuclear repositioning from a V(D)J recombination-repressive compartment to a permissive one. E34-induced nuclear repositioning of the E34 subTAD promoted Vκ-Jκ interactions assisted by enhancer-associated epigenetic marks and de novo CTCF binding. Finally, we found that E34-instructed Vκ-Jκ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. These data show how enhancer-instructed chromatin topology mechanically pulls specific Vκ and Jκ genes into close physical proximity to generate distinct antibody repertoires to combat bacterial infection.
2022-12-05 | GSE193813 | GEO
Project description:Antigen receptor loci are organized into variable (V), diversity (D), and joining (J) elements that rearrange to generate diverse antigen receptor repertoires. Here, we identified an enhancer (E34) in the immunoglobulin kappa locus (Igκ) that instructed rearrangement of Vκ genes located in a sub-topologically associating domain (subTAD), including a Vκ gene encoding for antibodies targeting bacterial phosphorylcholine. E34 promoted the deposition of active histone marks across the E34 subTAD to instruct its nuclear repositioning from a V(D)J recombination-repressive compartment to a permissive one. E34-induced nuclear repositioning of the E34 subTAD promoted Vκ-Jκ interactions assisted by enhancer-associated epigenetic marks and de novo CTCF binding. Finally, we found that E34-instructed Vκ-Jκ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. These data show how enhancer-instructed chromatin topology mechanically pulls specific Vκ and Jκ genes into close physical proximity to generate distinct antibody repertoires to combat bacterial infection.
2022-12-05 | GSE193967 | GEO
Project description:Antigen receptor loci are organized into variable (V), diversity (D), and joining (J) elements that rearrange to generate diverse antigen receptor repertoires. Here, we identified an enhancer (E34) in the immunoglobulin kappa locus (Igκ) that instructed rearrangement of Vκ genes located in a sub-topologically associating domain (subTAD), including a Vκ gene encoding for antibodies targeting bacterial phosphorylcholine. E34 promoted the deposition of active histone marks across the E34 subTAD to instruct its nuclear repositioning from a V(D)J recombination-repressive compartment to a permissive one. E34-induced nuclear repositioning of the E34 subTAD promoted Vκ-Jκ interactions assisted by enhancer-associated epigenetic marks and de novo CTCF binding. Finally, we found that E34-instructed Vκ-Jκ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. These data show how enhancer-instructed chromatin topology mechanically pulls specific Vκ and Jκ genes into close physical proximity to generate distinct antibody repertoires to combat bacterial infection.
2022-12-05 | GSE193846 | GEO
Project description:Antigen receptor loci are organized into variable (V), diversity (D), and joining (J) elements that rearrange to generate diverse antigen receptor repertoires. Here, we identified an enhancer (E34) in the immunoglobulin kappa locus (Igκ) that instructed rearrangement of Vκ genes located in a sub-topologically associating domain (subTAD), including a Vκ gene encoding for antibodies targeting bacterial phosphorylcholine. E34 promoted the deposition of active histone marks across the E34 subTAD to instruct its nuclear repositioning from a V(D)J recombination-repressive compartment to a permissive one. E34-induced nuclear repositioning of the E34 subTAD promoted Vκ-Jκ interactions assisted by enhancer-associated epigenetic marks and de novo CTCF binding. Finally, we found that E34-instructed Vκ-Jκ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. These data show how enhancer-instructed chromatin topology mechanically pulls specific Vκ and Jκ genes into close physical proximity to generate distinct antibody repertoires to combat bacterial infection.
2022-12-05 | GSE193822 | GEO