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The Ets factor Spi-B is a direct critical target of the coactivator OBF-1.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2006 Aug 01; Vol. 103 (31), pp. 11665-70. Date of Electronic Publication: 2006 Jul 21. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Animals
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Humans
In Situ Hybridization
Mice
Mice, Transgenic
Oligonucleotide Array Sequence Analysis
Phenotype
Proto-Oncogene Proteins c-ets genetics
Receptors, Antigen, B-Cell metabolism
Signal Transduction physiology
T-Lymphocytes metabolism
Trans-Activators genetics
Transcription Factors genetics
Transcription Factors metabolism
Proto-Oncogene Proteins c-ets metabolism
Trans-Activators metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 103
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 16861304
- Full Text :
- https://doi.org/10.1073/pnas.0509430103