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Three‐dimensional architecture of the IgH locus facilitates class switch recombination
Author(s) -
Kenter Amy L.,
Feldman Scott,
Wuerffel Robert,
Achour Ikbel,
Wang Lili,
Kumar Satyendra
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06604.x
Subject(s) - chromatin , immunoglobulin class switching , enhancer , rna polymerase ii , biology , transcription (linguistics) , dna , genetics , promoter , effector , recombination , v(d)j recombination , microbiology and biotechnology , transcription factor , gene , gene expression , b cell , antibody , linguistics , philosophy
Immunoglobulin (Ig) class switch recombination (CSR) is responsible for diversification of antibody effector function during an immune response. This region‐specific recombination event, between repetitive switch (S) DNA elements, is unique to B lymphocytes and is induced by activationinduced deaminase (AID). CSR is critically dependent on transcription of noncoding RNAs across S regions. However, mechanistic insight regarding this process has remained unclear. New studies indicate that long‐range intrachromosomal interactions among IgH transcriptional elements organize the formation of the S/S synaptosome, as a prerequisite for CSR. This three‐dimensional chromatin architecture simultaneously brings promoters and enhancers into close proximity to facilitate transcription. Here, we recount how transcription across S DNA promotes accumulation of RNA polymerase II, leading to the introduction of activating chromatin modifications and hyperaccessible chromatin that is amenable to AID activity.