ArticleFrontiers in immunology2018
Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vκ Gene Rearrangement in Pre-B Cells and Pro-B Cells.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Exuberant long noncoding RNA expression may sculpt Igh locus topology.Frontiers in immunology · 2025Article
- Article
- EBF1, PAX5, and MYC: regulation on B cell development and association with hematologic neoplasms.Frontiers in immunology · 2024Review
- Enhancers within the Ig V Gene Region Orchestrate Chromatin Topology and Regulate V Gene Rearrangement Frequency to Shape the B Cell Receptor Repertoire Specificities.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Multiple lineage-specific epigenetic landscapes at the antigen receptor loci.Aging research (Hong Kong, China) · 2023Article
- Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.Nature communications · 2023Article
- Locus architecture and RAG scanning determine antibody diversity.Trends in immunology · 2023Review
- Enhancer-instructed epigenetic landscape and chromatin compartmentalization dictate a primary antibody repertoire protective against specific bacterial pathogens.Nature immunology · 2023Article
- Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination.Immunological reviews · 2022Review
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- Igh Locus Polymorphism May Dictate Topological Chromatin Conformation and V Gene Usage in the Ig Repertoire.Frontiers in immunology · 2021Review
- V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation.Immunology · 2020Review
- Enhancers as regulators of antigen receptor loci three-dimensional chromatin structure.Transcription · 2020Review
- Selected before selection: A case for inherent antigen bias in the T cell receptor repertoire.Current opinion in systems biology · 2019Article
- New insights emerge as antibody repertoire diversification meets chromosome conformation.F1000Research · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
To date there has not been a study directly comparing relative Igκ rearrangement frequencies obtained from genomic DNA (gDNA) and cDNA and since each approach has potential biases, this is an important issue to clarify. Here we used deep sequencing to compare the unbiased gDNA and RNA Igκ repertoire from the same pre-B cell pool. We find that ~20% of Vκ genes have rearrangement frequencies ≥2-fold up or down in RNA vs. DNA libraries, including many members of the Vκ3, Vκ4, and Vκ6 families. Regression analysis indicates Ikaros and E2A binding are associated with strong promoters. Within the pre-B cell repertoire, we observed that individual Vκ genes rearranged at very different frequencies, and also displayed very different Jκ usage. Regression analysis revealed that the greatly unequal Vκ gene rearrangement frequencies are best predicted by epigenetic marks of enhancers. In particular, the levels of newly arising H3K4me1 peaks associated with many Vκ genes in pre-B cells are most predictive of rearrangement levels. Since H3K4me1 is associated with long range chromatin interactions which are created during locus contraction, our data provides mechanistic insight into unequal rearrangement levels. Comparison of Igκ rearrangements occurring in pro-B cells and pre-B cells from the same mice reveal a pro-B cell bias toward usage of Jκ-distal Vκ genes, particularly Vκ10-96 and Vκ1-135. Regression analysis indicates that PU.1 binding is the highest predictor of Vκ gene rearrangement frequency in pro-B cells. Lastly, the repertoires of iEκ
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