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Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection

ABSTRACT: Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection

PROVIDER: PRJNA798659 | ENA |

REPOSITORIES: ENA

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Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [ATAC-seq]

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

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [Hi-C]

2022-12-05 | GSE193967 | GEO

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [RNA-seq]

2022-12-05 | GSE193846 | GEO

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [CUT&RUN]

2022-12-05 | GSE193822 | GEO

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [Hi-C]

Project description:Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [Hi-C]

| PRJNA798665 | ENA

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [CUT&RUN]

Project description:Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [CUT&RUN]

| PRJNA798041 | ENA

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [ATAC-seq]

Project description:Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [ATAC-seq]

| PRJNA798026 | ENA

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [RNA-seq]

Project description:Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection [RNA-seq]

| PRJNA798079 | ENA

Enhancer-instructed chromatin folding and compartmentalization dictate Vκ repertoire rearrangement to combat bacterial infection

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

2022-12-05 | GSE193968 | GEO

Enhancer-instructed epigenetic landscape and chromatin compartmentalization dictate a primary antibody repertoire protective against specific bacterial pathogens.

Project description:Antigen receptor loci are organized into variable (V), diversity (D) and joining (J) gene segments that rearrange to generate antigen receptor repertoires. Here, we identified an enhancer (E34) in the murine immunoglobulin kappa (Igk) locus that instructed rearrangement of Vκ genes located in a sub-topologically associating domain, including a Vκ gene encoding for antibodies targeting bacterial phosphorylcholine. We show that E34 instructs the nuclear repositioning of the E34 sub-topologically associating domain from a recombination-repressive compartment to a recombination-permissive compartment that is marked by equivalent activating histone modifications. Finally, we found that E34-instructed Vκ-Jκ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. We propose that the merging of Vκ genes with Jκ elements is instructed by one-dimensional epigenetic information imposed by enhancers across Vκ and Jκ genomic regions. The data also reveal how enhancers generate distinct antibody repertoires that provide protection against lethal bacterial infection.

| S-EPMC10917333 | biostudies-literature

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