Dissociation of Pax-5 from KI and KII sites during kappa-chain gene rearrangement correlates with its association with the underphosphorylated form of retinoblastoma.
The KI and KII sites play a crucial role in kappa-chain gene rearrangement, which was investigated in mice deficient for these sites. Previously, we found that Pax-5 can bind to the KI and KII sites; however, the function of Pax-5 in kappa-chain gene rearrangement has not been investigated. Here, we have used an in vitro culture system in which differentiation from pre-B cells to immature B cells is induced by removing IL-7. We showed that, after the induction of differentiation, Pax-5 dissociated from the KI and KII revealed by EMSA analyses, and this dissociation occurred specifically at the KI and KII sites, but not at the Pax-5 binding site, in the CD19 promoter because of a lower binding affinity of Pax-5 for the KI and KII sites. During differentiation induced by removing IL-7, the underphosphorylated form of retinoblastoma preferentially associated with Pax-5, which caused dissociation of Pax-5 from KI and KII sites. These results suggest that the dissociation of Pax-5 from the KI and KII sites is important in the induction of kappa-chain gene rearrangement.
Sato
H
H
Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8501 Japan.
Wang
D
D
Kudo
A
A
D020816:Amino Acid Motifs; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051757:PAX5 Transcription Factor; D010766:Phosphorylation; D054420:Pre-B Cell Receptors; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D008562:Membrane Glycoproteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D016160:Retinoblastoma Protein; D014157:Transcription Factors