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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
Rao ,
Lee Ann
Garrett-Sinha¶,
Jung
Yoon¶, and
M. Celeste
Simon¶
From the Department of Pathology, ¶ Howard
Hughes Medical Institute, and the 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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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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