GATA-2 and GATA-2/ER display opposing activities in the development and differentiation of blood progenitors

摘要

GATA-2 is a zinc finger transcription factor essential for the development of hematopoiesis. While GATA-2 is generally considered to play an important role in the biology of hematopoietic stem and progenitor cells, its function within these compartments is not well understood. Here we have employed both conditional expression of GATA-2 and conditional activation of a GATA-2/estrogen receptor (ER) chimera to examine the effect of enforced GATA-2 expression in the development and differentiation of hematopoietic progenitors from murine embryonic stem cells. Consistent with the phenotype of GATA-2 null animals, conditional expression of GATA-2 from a tetracycline-inducible promoter enhanced the production of hematopoietic progenitors. Conditional activation of a GATA-2/ER chimera produced essentially opposite effects to those observed with conditional GATA-2 expression. GATA-2 and GATA-2/ER differ in their binding activities and transcriptional interactions from other hematopoietic-associated transcription factors such as c-Myb and PU.1. While we have exploited these differences in activity to explore the transcriptional networks underlying hematopoietic cell fate determination, our results suggest that care should be taken in interpreting results obtained using only chimeric proteins.