ArticleProceedings of the National Academy of Sciences of the United States of America2011
CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 209 citations in OpenAlex.
- Trial
- Transcription factors as drivers of 3D enhancer-promoter interactions.Current opinion in structural biology · 2026Review
- CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination.Nucleic acids research · 2026Article
- B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing.bioRxiv : the preprint server for biology · 2026Article
- Dynamic O-GlcNAcylation governs long-range chromatin interactions in V(D)J recombination during early B-cell development.Cellular & molecular immunology · 2025Article
- Exuberant long noncoding RNA expression may sculpt Igh locus topology.Frontiers in immunology · 2025Article
- Untangling the loops ofLeukemia & lymphoma · 2025Review
- Fdo1, Fkh1, Fkh2, and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae.Genetics · 2024Article
- YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle.Nature genetics · 2024Article
- Yin Yang 1 regulates cohesin complex protein SMC3 in mouse hematopoietic stem cells.Blood advances · 2024Article
- Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development.Nature genetics · 2024Article
- Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.Nucleic acids research · 2023Article
- Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes.Cell reports · 2023Article
- Three-way contact analysis characterizes the higher order organization of the Tcra locus.Nucleic acids research · 2023Article
- 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
- Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.Nature communications · 2023Article
- Three-Dimensional Chromatin Structure of the EBV Genome: A Crucial Factor in Viral Infection.Viruses · 2023Review
- An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation.Nature communications · 2023Article
- Locus architecture and RAG scanning determine antibody diversity.Trends in immunology · 2023Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly responsible for this are unknown. Because CCCTC-binding factor (CTCF) has been demonstrated to be involved in long-range chromosomal interactions, we hypothesized that CTCF may promote the contraction of the Igh locus. ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. To test whether CTCF was involved in locus compaction, we used 3D-FISH to measure compaction in pro-B cells transduced with CTCF shRNA retroviruses. Reduction of CTCF binding resulted in a decrease in Igh locus compaction. Long-range interactions within the Igh locus were measured with the chromosomal conformation capture assay, revealing direct interactions between CTCF sites 5' of DFL16 and the 3' regulatory region, and also the intronic enhancer (Eμ), creating a D(H)-J(H)-Eμ-C(H) domain. Knockdown of CTCF also resulted in the increase of antisense transcription throughout the D(H) region and parts of the V(H) locus, suggesting a widespread regulatory role for CTCF. Together, our findings demonstrate that CTCF plays an important role in the 3D structure of the Igh locus and in the regulation of antisense germline transcription and that it contributes to the compaction of the Igh locus.
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