@article{1996849c488b44929c276f57e4aef2f8,
title = "Transcription factor Pax5 (BSAP) transactivates the RAG-mediated VH-to-DJH rearrangement of immunoglobulin genes",
abstract = "Immunoglobulin rearrangement from variable heavy chain (VH) to diversity (D)-joining heavy chain (JH), which occurs exclusively in B lineage cells, is impaired in mice deficient for the B lineage-specific transcription factor Pax5. Conversely, ectopic Pax5 expression in thymocytes promotes the rearrangement of DH -proximal VH7183 genes. In exploring the mechanism for Pax5 regulation of VH-to-DJH recombination, we have identified multiple Pax5 binding sites in the coding regions of human and mouse VH gene segments. Pax5 bound to those sites in vitro and occupied VH genes in early human and mouse B lineage cells. Moreover, Pax5 interacted with the recombination-activating gene 1 (RAG1)-RAG2 complex to enhance RAG-mediated VH recombination signal sequence cleavage and recombination of a VH gene substrate. These findings indicate a direct activating function for Pax5 in RAG-mediated immunoglobulin VH-to-DJH recombination.",
author = "Zhixin Zhang and Espinoza, {Celia R.} and Zhihong Yu and Robert Stephan and Ti He and Williams, {G. Stuart} and Burrows, {Peter D.} and James Hagman and Feeney, {Ann J.} and Cooper, {Max D.}",
note = "Funding Information: We thank M. Busslinger (Research Institute of Molecular Pathology, Vienna, Austria) for the Pax5 expression vectors and discussions; D. Roth (Baylor College of Medicine, Houston, Texas), M. Gellert (National Institutes of Health, Bethesda, Maryland) and D. Schatz (Yale University, New Haven, Connecticut) for the pEBG-RAG1, pEBG-RAG2, pJH289 and pJH290 vectors, protocols for RAG protein purification and in vitro cleavage assays, and discussions; S. Desiderio (Johns Hopkins University, Baltimore, Maryland) for antibodies to RAG1 and RAG2, pCDNA1-RAG1 and pCDNA1-RAG2 expression vectors, and suggestions; Y. Kubagawa for DNA sequencing; and members of the laboratories of M.D.C., Z.Z., A.J.F. and J.H. for discussions. Supported by the National Institutes of Health (AI39816 and AI48098; AI56322, AI54661 and CA107478 to J.H.; and AI52313 to the laboratory of A.J.F.), the National Institutes of Health– National Institute of Arthritis, Musculoskeletal and Skin Diseases (K01 AR048592 to Z.Z.) and the Howard Hughes Medical Institute (M.D.C.).",
year = "2006",
month = jun,
doi = "10.1038/ni1339",
language = "English (US)",
volume = "7",
pages = "616--624",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Research",
number = "6",
}