Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse bone marrow with Aiolos and OBF-1 deletions from 7 week old mice


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 l5l5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the l5l5 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. OBF-1 or Aiolos or both were deleted and the gene expression profiles for these animals investigated using Affymetrix arrays Experiment Overall Design: Two control wildtype animals, then duplicates for each of the single Aiolos or OBF-1 mutants and further duplicates for the Aiolos/OBF-1 double mutants

ORGANISM(S): Mus musculus

SUBMITTER: Edward James Oakeley 

PROVIDER: E-GEOD-12356 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Silencing and nuclear repositioning of the lambda5 gene locus at the pre-B cell stage requires Aiolos and OBF-1.

Karnowski Alexander A   Cao Chun C   Matthias Gabriele G   Carotta Sebastian S   Corcoran Lynn M LM   Martensson Inga-Lill IL   Skok Jane A JA   Matthias Patrick P  

PloS one 20081030 10


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  ...[more]

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