First Author | Bartholdy B | Year | 2006 |
Journal | Proc Natl Acad Sci U S A | Volume | 103 |
Issue | 31 | Pages | 11665-70 |
PubMed ID | 16861304 | Mgi Jnum | J:111795 |
Mgi Id | MGI:3654861 | Doi | 10.1073/pnas.0509430103 |
Citation | Bartholdy B, et al. (2006) The Ets factor Spi-B is a direct critical target of the coactivator OBF-1. Proc Natl Acad Sci U S A 103(31):11665-70 |
abstractText | OBF-1 (Bob.1, OCA-B) is a lymphoid-specific transcriptional coactivator that associates with the transcription factors Oct-1 or Oct-2 on the conserved octamer element present in the promoters of several ubiquitous and lymphoid-specific genes. OBF-1-deficient mice have B cell-intrinsic defects, lack germinal centers, and have severely impaired immune responses to T cell-dependent antigens. Crucial genes that are regulated by OBF-1 and that might explain the observed phenotype of OBF-1 deficiency have remained elusive to date. Here we have generated transgenic mice expressing OBF-1 specifically in T cells and examined these together with mice lacking OBF-1 to discover transcriptional targets of this coactivator. Using microarray analysis, we have identified the Ets transcription factor Spi-B as a direct target gene critically regulated by OBF-1 that can help explain the phenotype of OBF-1-deficient mice. Spi-B has been implicated in signaling pathways downstream of the B cell receptor and is essential for germinal center formation and maintenance. The present findings establish a hierarchy between these two factors and provide a molecular link between OBF-1 and B cell receptor signaling. |