The Ets factor Spi-B is a direct critical target of the coactivator OBF-1

Boris A. Bartholdy, Camille Du Roure, Alain Bordon, Dianne Emslie, Lynn M. Corcoran, Patrick Matthias

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)11665-11670
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number31
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Fingerprint

B-Lymphocytes
Germinal Center
Octamer Transcription Factor-1
Proto-Oncogene Proteins c-ets
Genes
T-Lymphocytes
Phenotype
Microarray Analysis
Transgenic Mice
Maintenance
Antigens
3'-(1-butylphosphoryl)adenosine

Keywords

  • B cell development
  • Gene regulation
  • Transcription factors
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The Ets factor Spi-B is a direct critical target of the coactivator OBF-1. / Bartholdy, Boris A.; Du Roure, Camille; Bordon, Alain; Emslie, Dianne; Corcoran, Lynn M.; Matthias, Patrick.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 31, 01.08.2006, p. 11665-11670.

Research output: Contribution to journalArticle

Bartholdy, Boris A. ; Du Roure, Camille ; Bordon, Alain ; Emslie, Dianne ; Corcoran, Lynn M. ; Matthias, Patrick. / The Ets factor Spi-B is a direct critical target of the coactivator OBF-1. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 31. pp. 11665-11670.
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