Enhancer-instructed epigenetic landscape and chromatin compartmentalization dictate a primary antibody repertoire protective against specific bacterial pathogens.
E Mauricio Barajas-MoraLindsay LeeHanbin LuJ Andrés ValderramaElisabet BjanesVictor NizetAnn J FeeneyMing HuCornelis MurrePublished in: Nature immunology (2023)
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 V κ genes located in a sub-topologically associating domain, including a V κ 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 V κ -J κ rearrangement was essential to combat Streptococcus pneumoniae but not methicillin-resistant Staphylococcus aureus or influenza infections. We propose that the merging of V κ genes with J κ elements is instructed by one-dimensional epigenetic information imposed by enhancers across V κ and J κ genomic regions. The data also reveal how enhancers generate distinct antibody repertoires that provide protection against lethal bacterial infection.
Keyphrases
- genome wide
- dna methylation
- copy number
- methicillin resistant staphylococcus aureus
- dna repair
- genome wide identification
- gene expression
- transcription factor
- binding protein
- dna damage
- staphylococcus aureus
- nuclear factor
- signaling pathway
- single cell
- genome wide analysis
- healthcare
- cancer therapy
- gram negative
- big data
- machine learning
- oxidative stress
- genome wide association study
- multidrug resistant
- antimicrobial resistance