Silencing and Nuclear Repositioning of the lambda 5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1
- Author(s)
- Karnowski, A; Cao, C; Matthias, G; Carotta, S; Corcoran, LM; Martensson, IL; Skok, JA; Matthias, P;
- Details
- Publication Year 2008-10-30,Volume 3,Issue #10,Page -
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- 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 lambda 5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the lambda 5 gene is impaired in pre-B cells lacking OBF-1 and Aiolos. These studies uncover a novel role for OBF-1 and Aiolos in controlling the transcription and nuclear organization of genes involved in pre-BCR function.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0003568
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-10-30 12:00:00