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J Biol Chem, Vol. 274, Issue 48, 34245-34252, November 26, 1999

The Ets Factors PU.1 and Spi-B Regulate the Transcription in Vivo of P2Y10, a Lymphoid Restricted Heptahelical Receptor

Sridhar RaoDagger , Lee Ann Garrett-Sinha, Jung Yoon, and M. Celeste Simonparallel

From the Dagger  Department of Pathology,  Howard Hughes Medical Institute, and the parallel  Departments of Medicine and Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637

To investigate the in vivo functions of PU.1 and Spi-B, two highly related Ets transcription factors, we previously generated PU.1+/+Spi-B-/- and PU.1+/-Spi-B-/- mice and demonstrated a significant decrease in B-cell receptor (BCR) signaling in mutants. Major components of BCR signaling appear to be expressed at normal levels in these mice, implying that PU.1 and Spi-B cooperate in the transcription of additional target genes important for antigen receptor signaling. We used subtractive hybridization to identify novel in vivo PU.1/Spi-B target genes and determined that the expression of a heptahelical receptor, P2Y10, is dramatically reduced in PU.1+/-Spi-B-/- B-cells. Further analysis shows that P2Y10 expression is restricted to lymphoid cells and parallels that of Spi-B in B-lymphocytes. Lastly, the P2Y10 promoter contains a PU.1/Spi-B binding site functionally required for efficient transcription in B-cells. Thus, P2Y10 is likely to be a direct in vivo transcriptional target for PU.1 and Spi-B and provides a unique model to explore transcriptional regulation by this Ets factor subfamily. Furthermore, P2Y10 suggests an intriguing connection between heterotrimeric G-proteins and BCR signaling.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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