title: The PU.1 and NF-EM5 binding motifs in the Igkappa 3' enhancer are responsible for directing somatic hypermutations to the intrinsic hotspots in the transgenic Vkappa gene.
abstract: Somatic hypermutation is a key mechanism in generating Ig with higher affinities to antigen, a process known as affinity maturation. Using Igkappa transgenes, the 3' enhancer (kappaE3') has been shown to play an important role in introducing hypermutations. In order to identify the cis-acting elements that regulate hypermutagenesis, we have generated transgenic substrates containing mutations/deletions in the kappaE3' region. Here, we report that base substitutions in the kappaE3', either in the PU.1 or in the NF-EM5 binding motif, not only reduce the mutation rate but also disrupt the directed mutagenesis in the intrinsic hotspots of the Igkappa transgene.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kodama
authors.forename: R
authors.initials: R
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Nishizumi
authors.forename: F
authors.initials: F
authors.lastname: Nagawa
authors.forename: T
authors.initials: T
authors.lastname: Takemori
authors.forename: H
authors.initials: H
authors.lastname: Sakano
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D005260:Female; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D020413:3' Untranslated Regions; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains