Passera ou ne passera pas—accessibility is key

Villartay, Jean‐Pierre de

doi:10.1038/ni1006-1019

Cited by 2 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One commentary [38] speculated on the connection between transcription, chromatin remodeling, and recruitment of RAG, pointing out that RAG2 contains a methyl lysine-binding region that may act as a reader for the histone code of the chromatin and thus may act differentially depending upon the pattern of the histone modifications. It is currently thought that the formation of a Ig/TCR promoter-enhancer holocomplex, consisting of a complex of nuclear factors-DNA interaction, directs the chromatin remodeling and DNA modifications that promote chromatin interaction with RAG [39,40].…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Heavy Chain Exclusion in the Shark

et al. 2008

View full text Add to dashboard Cite

The adaptive immune system depends on specific antigen receptors, immunoglobulins (Ig) in B lymphocytes and T cell receptors (TCR) in T lymphocytes. Adaptive responses to immune challenge are based on the expression of a single species of antigen receptor per cell; and in B cells, this is mediated in part by allelic exclusion at the Ig heavy (H) chain locus. How allelic exclusion is regulated is unclear; we considered that sharks, the oldest vertebrates possessing the Ig/TCR-based immune system, would yield insights not previously approachable and reveal the primordial basis of the regulation of allelic exclusion. Sharks have an IgH locus organization consisting of 15–200 independently rearranging miniloci (VH-D1-D2-JH-Cμ), a gene organization that is considered ancestral to the tetrapod and bony fish IgH locus. We found that rearrangement takes place only within a minilocus, and the recombining gene segments are assembled simultaneously and randomly. Only one or few H chain genes were fully rearranged in each shark B cell, whereas the other loci retained their germline configuration. In contrast, most IgH were partially rearranged in every thymocyte (developing T cell) examined, but no IgH transcripts were detected. The distinction between B and T cells in their IgH configurations and transcription reveals a heretofore unsuspected chromatin state permissive for rearrangement in precursor lymphocytes, and suggests that controlled limitation of B cell lineage-specific factors mediate regulated rearrangement and allelic exclusion. This regulation may be shared by higher vertebrates in which additional mechanistic and regulatory elements have evolved with their structurally complex IgH locus.

show abstract

Section: Discussionmentioning

confidence: 99%