Transcriptomics

Dataset Information

38

RAG-mediated DNA double strand breaks activate a cell-type-specific checkpoint to inhibit pre-B cell receptor signals


ABSTRACT: Pre-B cell receptor (pre-BCR) signals initiate immunoglobulin light (Igl) chain gene assembly leading to RAG-mediated DNA double-strand breaks (DSBs). These signals also promote cell cycle entry, which could cause aberrant DSB repair and genome instability in pre-B cells. Here we show that RAG DSBs inhibit pre-BCR signals through the ATM- and NF-κB2-dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor to prevent the pre-BCR from inducing additional Igl chain gene rearrangements and driving pre-B cells with RAG DSBs into cycle. We propose that pre-B cells toggle between pre-BCR signals and this RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes. Overall design: Three independent IL-7 cultures for each genotype (Rag1-/-:μIgH:Bcl2, Art-/-:μIgH:Bcl2 and Art-/-:Nfkb2-/-:μIgH:Bcl2) were withdrawn from IL-7 for 2 days. RNA was isolated using RNeasy (Qiagen). Gene expression profiling was performed using Illumina MouseRef-8 expression microarrays.

INSTRUMENT(S): Illumina MouseRef-8 v2.0 expression beadchip

ORGANISM(S): Mus musculus  

SUBMITTER: Jeffrey J Bednarski  

PROVIDER: GSE67854 | GEO |

SECONDARY ACCESSION(S): PRJNA281075

REPOSITORIES: GEO

Similar Datasets

2016-01-13 | E-GEOD-67854 | ArrayExpress
1000-01-01 | S-EPMC4749927 | BioStudies
1000-01-01 | S-EPMC5360515 | BioStudies
1000-01-01 | S-EPMC2040436 | BioStudies
2016-01-01 | S-EPMC6299834 | BioStudies
2019-01-01 | S-EPMC6898044 | BioStudies
2019-01-01 | S-EPMC6870970 | BioStudies
1000-01-01 | S-EPMC4333404 | BioStudies
2011-01-01 | S-EPMC3145022 | BioStudies
2013-01-01 | S-EPMC3807868 | BioStudies