Silencing and nuclear repositioning of the λ5 gene locus at the pre-B cell stage requires Aiolos and OBF-1

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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 λ5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the λ5 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. © 2008 Karnowski et al.

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Karnowski, A., Cao, C., Matthias, G., Carotta, S., Corcoran, L. M., Martensson, I. L., … Matthias, P. (2008). Silencing and nuclear repositioning of the λ5 gene locus at the pre-B cell stage requires Aiolos and OBF-1. PLoS ONE, 3(10). https://doi.org/10.1371/journal.pone.0003568

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