silencing and nuclear repositioning of the λ5 gene locus at the pre-b cell stage requires aiolos and obf-1λ5基因的沉默和核重新定位轨迹在前b细胞阶段需要艾俄洛斯和obf-1.pdfVIP

Silencing and Nuclear Repositioning of the l5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1 1,2 1 1 2 2 Alexander Karnowski , Chun Cao , Gabriele Matthias , Sebastian Carotta , Lynn M. Corcoran , Inga-Lill 3 4,5 1 Martensson , Jane A. Skok , Patrick Matthias * 1 Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland, 2 The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, 3 Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom, 4 Department of Immunology and Molecular Pathology, University College London, London, United Kingdom, 5 New York University School of Medicine, New York, New York, United States of America Abstract The chromatin regulator Aiolos and the transcriptional coactivator OBF-1 have been implicated in regulating aspects of B cell maturation and activation. Mice lacking either of these factors have a largely normal early B cell development. However, when both factors are eliminated simultaneously a block is uncovered at the transition between pre-B and immature B cells, indicating that these proteins exert a critical function in developing B lymphocytes. In mice deficient for Aiolos and OBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulin light chain DNA rearrangement is observed. We identified genes whose expression is deregulated in the pre-B cell compartment of these mice. In particular, we found that components of the pre-BCR, such as the surrogate light chain genes l5