ArticleProceedings of the National Academy of Sciences of the United States of America2012
Noncoding transcription within the Igh distal V(H) region at PAIR elements affects the 3D structure of the Igh locus in pro-B cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 106 citations in OpenAlex.
- A hierarchy of spatial confinements governs chromatin dynamics and genomic encounters.bioRxiv : the preprint server for biology · 2026Article
- CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination.Nucleic acids research · 2026Article
- Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in AppAging cell · 2025Article
- Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination.Cell reports · 2025Article
- Exuberant long noncoding RNA expression may sculpt Igh locus topology.Frontiers in immunology · 2025Article
- YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle.Nature genetics · 2024Article
- UPF1 plays critical roles in early B cell development.Nature communications · 2024Article
- Locus folding mechanisms determine modes of antigen receptor gene assembly.The Journal of experimental medicine · 2024Article
- Multiple lineage-specific epigenetic landscapes at the antigen receptor loci.Aging research (Hong Kong, China) · 2023Article
- Enhancers of the PAIR4 regulatory module promote distal VThe EMBO journal · 2023Article
- Long Non-Coding RNA Signatures in Lymphopoiesis and Lymphoid Malignancies.Non-coding RNA · 2023Review
- Contribution of the IGCR1 regulatory element and the 3'Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation.Nature communications · 2023Article
- The role of chromatin loop extrusion in antibody diversification.Nature reviews. Immunology · 2022Review
- Coming full circle: On the origin and evolution of the looping model for enhancer-promoter communication.The Journal of biological chemistry · 2022Review
- Evolving Views of Long Noncoding RNAs and Epigenomic Control of Lymphocyte State and Memory.Cold Spring Harbor perspectives in biology · 2022Review
- V(D)J Recombination: Recent Insights in Formation of the Recombinase Complex and Recruitment of DNA Repair Machinery.Frontiers in cell and developmental biology · 2022Review
- Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination.Immunological reviews · 2022Review
- Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives.Biomedicines · 2021Review
- Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Noncoding sense and antisense germ-line transcription within the Ig heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germ-line transcription throughout the Igh locus has been done. Therefore, we performed directional RNA-seq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two Pax5-activated intergenic repeat (PAIR) elements in the distal IghV region. Importantly, long-distance loops measured by chromosome conformation capture (3C) are observed between these two active PAIR promoters and Eμ, the start site of Iμ germ-line transcription, in a lineage- and stage-specific manner, even though this antisense transcription is Eμ-independent. YY1(-/-) pro-B cells are greatly impaired in distal V(H) gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-Eμ interactions. ChIP-seq shows high level YY1 binding only at Eμ, but low levels near some antisense promoters. PAIR-Eμ interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat-shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal V(H) genes close to the DJ(H) rearrangement which is adjacent to Eμ. Therefore, we hypothesize that one key role of noncoding germ-line transcription is to facilitate locus compaction, allowing distal V(H) genes to undergo efficient rearrangement.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.