title: A major deletion in the Vκ-Jκ intervening region results in hyperelevated transcription of proximal Vκ genes and a severely restricted repertoire.
abstract: Our previous studies have shown that DNase I hypersensitive sites 1 and 2 (HS1-2) and HS3-6 within the mouse Vκ-Jκ intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire. In this article, we demonstrate that a 6.3-kb deletion encompassing HS1-6 altogether not only leads to the predictable sums of these phenotypes, but also results in a novel hyperelevation of transcription of proximal Vκ genes, in both pre-B and splenic B cells. These findings reveal previously unrecognized additional functions for cis-elements within the Vκ-Jκ intervening region, namely, prevention of the production of massive levels of noncoding RNA species by silencing transcription of germline proximal Vκ genes in both developing and mature B cells.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, People's Republic of China.
authors.forename: Yougui
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
authors.forename: Sung-Kyun
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and william.garrard@utsw.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Garrard
mesh_terms: D000818:Animals; D020868:Gene Silencing / Q000276:immunology; D007133:Immunoglobulin Joining Region / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D022661:RNA, Untranslated / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology*
chemical_list: D007133:Immunoglobulin Joining Region; D007145:Immunoglobulin kappa-Chains; D022661:RNA, Untranslated