| First Author | Soodgupta D | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 4 | Pages | 829-843.e5 |
| PubMed ID | 31644907 | Mgi Jnum | J:287248 |
| Mgi Id | MGI:6391592 | Doi | 10.1016/j.celrep.2019.09.026 |
| Citation | Soodgupta D, et al. (2019) RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex. Cell Rep 29(4):829-843.e5 |
| abstractText | Early B cell development is regulated by stage-specific transcription factors. PU.1, an ETS-family transcription factor, is essential for coordination of early B cell maturation and immunoglobulin gene (Ig) rearrangement. Here we show that RAG DNA double-strand breaks (DSBs) generated during Ig light chain gene (Igl) rearrangement in pre-B cells induce global changes in PU.1 chromatin binding. RAG DSBs activate a SPIC/BCLAF1 transcription factor complex that displaces PU.1 throughout the genome and regulates broad transcriptional changes. SPIC recruits BCLAF1 to gene-regulatory elements that control expression of key B cell developmental genes. The SPIC/BCLAF1 complex suppresses expression of the SYK tyrosine kinase and enforces the transition from large to small pre-B cells. These studies reveal that RAG DSBs direct genome-wide changes in ETS transcription factor activity to promote early B cell development. |
