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

doi:10.1073/pnas.0509430103

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

*Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; and
^‡The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia

Edited by Richard A. Flavell, Yale University School of Medicine, New Haven, CT, and approved June 15, 2006 (received for review December 6, 2005)

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.

Footnotes

^§To whom correspondence should be addressed. E-mail: patrick.matthias{at}fmi.ch
↵ ^†Present address: Division of Hematology/Oncology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
Author contributions: B.B., C.D.R., A.B., and P.M. designed research; B.B., C.D.R., A.B., and D.E. performed research; D.E. and L.M.C. contributed new reagents/analytic tools; B.B., C.D.R., A.B., and P.M. analyzed data; and B.B. and P.M. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

BCR,

B cell receptor;

GC,

germinal center;

PMA,

phorbol myristic acetate (phorbol 12-tetradecanoate 13-acetate12-O-tetradecanoylphorbol-13-acetate);

Pn,

promoter n;

PNA,

peanut agglutinin;

TD,

T cell-dependent.
Freely available online through the PNAS open access option.