Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates.
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.
Walsh
Jonathan C
JC
Department of Pharmacology and Physiological Sciences, The University of Chicago, IL 60637, USA.
DeKoter
Rodney P
RP
Lee
Hyun Jun
HJ
Smith
Erica D
ED
Lancki
David W
DW
Gurish
Michael F
MF
Friend
Daniel S
DS
Stevens
Richard L
RL
Anastasi
John
J
Singh
Harinder
H
D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D050989:GATA2 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008407:Mast Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D038042:Myelopoiesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D016335:Zinc Fingers; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C494712:Gata2 protein, mouse