The Ets Factor Spi-b is a Direct Critical Target of the Coactivator Obf-1.
From: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Aug 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 31
- Pages: 11665-70
- Medium: Print
- Language: English
- Citation (JAMA): Bartholdy Boris, Du Roure Camille, Bordon Alain, et al. The Ets Factor Spi-b is a Direct Critical Target of the Coactivator Obf-1.. Proc. Natl. Acad. Sci. U.S.A. Aug 2006;103:11665-70
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.
Mesh Headings (Keywords): Animals, DNA-Binding Proteins, Humans, In Situ Hybridization, Mice, Mice, Transgenic, Oligonucleotide Array Sequence Analysis, Phenotype, Proto-Oncogene Proteins c-ets, Receptors, Antigen, B-Cell, Signal Transduction, T-Lymphocytes, Trans-Activators, Transcription Factors, Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 16861304
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