ArticleMolecular and cellular biology2015
Insertion of an imprinted insulator into the IgH locus reveals developmentally regulated, transcription-dependent control of V(D)J recombination.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- The transgenic IG-DMR sequence of the mouse Dlk1-Dio3 domain acquired imprinted DNA methylation during the post-fertilization period.Epigenetics & chromatin · 2023Article
- Associations between Allelic Variants of the Human IgH 3' Regulatory Region 1 and the Immune Response to BNT162b2 mRNA Vaccine.Vaccines · 2021Article
- Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.Nucleic acids research · 2020Article
- Review
- Developmental regulation of DNA cytosine methylation at the immunoglobulin heavy chain constant locus.PLoS genetics · 2019Article
- Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory Element.Molecular and cellular biology · 2015Article
- Complete cis Exclusion upon Duplication of the Eμ Enhancer at the Immunoglobulin Heavy Chain Locus.Molecular and cellular biology · 2015Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The assembly of antigen receptor loci requires a developmentally regulated and lineage-specific recombination between variable (V), diversity (D), and joining (J) segments through V(D)J recombination. The process is regulated by accessibility control elements, including promoters, insulators, and enhancers. The IgH locus undergoes two recombination steps, D-J(H) and then V(H)-DJ(H), but it is unclear how the availability of the DJ(H) substrate could influence the subsequent V(H)-DJ(H) recombination step. The Eμ enhancer plays a critical role in V(D)J recombination and controls a set of sense and antisense transcripts. We epigenetically perturbed the early events at the IgH locus by inserting the imprinting control region (ICR) of the Igf2/H19 locus or a transcriptional insulator devoid of the imprinting function upstream of the Eμ enhancer. The insertions recapitulated the main epigenetic features of their endogenous counterparts, including differential DNA methylation and binding of CTCF/cohesins. Whereas the D-J(H) recombination step was unaffected, both the insulator insertions led to a severe impairment of V(H)-DJ(H) recombination. Strikingly, the inhibition of V(H)-DJ(H) recombination correlated consistently with a strong reduction of DJ(H) transcription and incomplete demethylation. Thus, developmentally regulated transcription following D-J(H) recombination emerges as an important mechanism through which the Eμ enhancer controls V(H)-DJ(H) recombination.
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