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PU.1 positively regulates GATA-1 expression in mast cells
Journal of Immunology
  • Clifford M. Takemoto, Johns Hopkins University
  • Stephanie Brandal, Johns Hopkins University
  • Anil G. Jegga, Cincinnati Children's Hospital Medical Center
  • Youl Nam Lee, Johns Hopkins University
  • Amir Shahlaee, University of Florida
  • Ye Ying, Johns Hopkins University
  • Rodney DeKoter, Western University
  • Michael A. McDevitt, Johns Hopkins University
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Coexpression of PU.1 and GATA-1 is required for proper specification of the mast cell lineage; however, in the myeloid and erythroid lineages, PU.1 and GATA-1 are functionally antagonistic. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. We isolated a variant mRNA isoform of GATA-1 in murine mast cells that is significantly upregulated during mast cell differentiation. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript. In contrast to erythroid and megakaryocyte cells, in mast cells we show that PU.1 and GATA-2 predominantly occupy potential cis-regulatory elements in the IB exon region in vivo. Using reporter assays, we identify an enhancer flanking the IB exon that is activated by PU.1. Furthermore, we observe that in PU.1 -/- fetal liver cells, low levels of the IE GATA-1 isoform is expressed, but the variant IB isoform is absent. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. Our results are consistent with a transcriptional hierarchy in which PU.1, possibly in concert with GATA-2, activates GATA-1 expression in mast cells in a pathway distinct from that seen in the erythroid and megakaryocytic lineages. Copyright © 2010 by The American Association of Immunologists, Inc.

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Clifford M. Takemoto, Stephanie Brandal, Anil G. Jegga, Youl Nam Lee, et al.. "PU.1 positively regulates GATA-1 expression in mast cells" Journal of Immunology Vol. 184 Iss. 8 (2010) p. 4349 - 4361
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