Faculty Collaboration Database

The Ets factors PU.1 and Spi-B regulate the transcription in vivo of P2Y10, a lymphoid restricted heptahelical receptor. J Biol Chem 1999 Nov 26;274(48):34245-52

Date

11/24/1999

Pubmed ID

10567398

DOI

10.1074/jbc.274.48.34245

Scopus ID

2-s2.0-0033607523 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

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.

Author List

Rao S, Garrett-Sinha LA, Yoon J, Simon MC

Author

Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3T3 Cells
Amino Acid Sequence
Animals
B-Lymphocytes
Binding Sites
Binding, Competitive
Blotting, Northern
Cell Lineage
DNA
DNA, Complementary
DNA-Binding Proteins
Gene Expression
Mice
Mice, Knockout
Molecular Sequence Data
Promoter Regions, Genetic
Proto-Oncogene Proteins
RNA, Messenger
Receptors, Antigen, B-Cell
Sequence Homology, Amino Acid
Tissue Distribution
Trans-Activators
Transcription Factors
Transcription, Genetic
Tumor Cells, Cultured