title: Three-dimensional architecture of the IgH locus facilitates class switch recombination.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois, USA. star1@uic.edu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kenter
authors.forename: Scott
authors.initials: S
authors.lastname: Feldman
authors.forename: Robert
authors.initials: R
authors.lastname: Wuerffel
authors.forename: Ikbel
authors.initials: I
authors.lastname: Achour
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Satyendra
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin; D003564:Cytidine Deaminase / Q000378:metabolism / Q000502:physiology; D020862:GC Rich Sequence; D056426:Genetic Loci; D006801:Humans; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains; D016296:Mutagenesis; D009154:Mutation; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D002843:Chromatin; D007143:Immunoglobulin Heavy Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase