title: The PU.1 binding site is a cis-element that regulates pro-B/pre-B specificity of Vkappa-Jkappa joining.
abstract: We have previously shown that the PU.1 binding motif (GAG GAA) in the 3'-enhancer region in the Ig kappa gene is responsible for the negative regulation of tissue (B/T)-specific Vkappa-Jkappa joining. Here we report that the PU.1 binding site also regulates the stage (pro-B/pre-B) specificity of Vkappa-Jkappa joining. In the substrate with base substitutions in the PU.1 binding motif, recombination took place in both pro-B (B220dull/CD43+) and pre-B (B220dull/CD43-) cells. In the transcriptional regulation, the PU.1 motif acts in a positive manner cooperatively with the nuclear factor-EM5 (or PIP) motif (GAAAAC), which is located 2 bp downstream from the PU.1 motif. Interestingly, base substitutions in the nuclear factor EM5 (PIP) motif did not affect the pro-B/pre-B specificity of Vkappa-Jkappa joining. Thus, the PU.1 motif regulates both temporal and tissue-specific rearrangements, while nuclear factor-EM5 is not involved in the regulation of Ig kappa recombination.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Takemori
authors.forename: M
authors.initials: M
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Tsuboi
authors.forename: F
authors.initials: F
authors.lastname: Nagawa
authors.forename: H
authors.initials: H
authors.lastname: Sakano
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006657:Histones / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D006657:Histones; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C073657:EM5 protein, Ensis minor; C061836:antigen T cell receptor, epsilon chain