title: S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase.
abstract: Molecular mechanisms underlying synapsis of activation-induced deaminase (AID)-targeted S regions during class switch recombination (CSR) are poorly understood. By using chromosome conformation capture techniques, we found that in B cells, the Emicro and 3'Ealpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activation led to recruitment of the germline transcript (GLT) promoters to the Emicro:3'Ealpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because Smicro was proximal to Emicro and a downstream S region was corecruited with the targeted GLT promoter to Emicro:3'Ealpha. We propose that GLT promoter association with the Emicro:3'Ealpha complex creates an architectural scaffolding that promotes S-S synapsis during CSR and that these interactions are stabilized by AID. Thus, the S-S synaptosome is formed as a result of the self-organizing transcription system that regulates GLT expression and may serve to guard against spurious chromosomal translocations.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wuerffel
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Fernando
authors.initials: F
authors.lastname: Grigera
authors.forename: John
authors.initials: J
authors.lastname: Manis
authors.forename: Erik
authors.initials: E
authors.lastname: Selsing
authors.forename: Thomas
authors.initials: T
authors.lastname: Perlot
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Michel
authors.initials: M
authors.lastname: Cogne
authors.forename: Eric
authors.initials: E
authors.lastname: Pinaud
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kenter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D023902:Chromosome Pairing / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase