Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates

Jonathan C. Walsh, Rodney P. DeKoter, Hyun Jun Lee, Erica D. Smith, David W. Lancki, Michael F. Gurish, Daniel S. Friend, Richard L. Stevens, John Anastasi, Harinder Singh*

*Corresponding author for this work

Research output: Contribution to journalArticle

209 Scopus citations

Abstract

PU.1 and GATA transcription factors appear to antagonize each other's function in the development of distinct lineages of the hematopoietic system. In contrast, we demonstrate that PU.1, like GATA-2, is essential for the generation of mast cells. PU.1-/- hematopoietic progenitors can be propagated in IL-3 and differentiate into mast cells or macrophages upon restoration of PU.1 activity. Using these progenitors and a conditionally activatable PU.1 protein, we show that PU.1 can negatively regulate expression of the GATA-2 gene. In the absence of GATA-2, PU.1 promotes macrophage but not mast cell differentiation. Reexpression of GATA-2 in such progenitors enables the generation of mast cells. We propose a developmental model in which cooperative function or antagonistic crossregulation by PU.1 of GATA-2 promotes distinct myeloid cell fates.

Original languageEnglish (US)
Pages (from-to)665-676
Number of pages12
JournalImmunity
Volume17
Issue number5
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates'. Together they form a unique fingerprint.

  • Cite this

    Walsh, J. C., DeKoter, R. P., Lee, H. J., Smith, E. D., Lancki, D. W., Gurish, M. F., Friend, D. S., Stevens, R. L., Anastasi, J., & Singh, H. (2002). Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates. Immunity, 17(5), 665-676. https://doi.org/10.1016/S1074-7613(02)00452-1