title: Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates.
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.
authors.affiliation: Department of Pharmacology and Physiological Sciences, The University of Chicago, IL 60637, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Walsh
authors.forename: Rodney P
authors.initials: RP
authors.lastname: DeKoter
authors.forename: Hyun Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Erica D
authors.initials: ED
authors.lastname: Smith
authors.forename: David W
authors.initials: DW
authors.lastname: Lancki
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gurish
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Friend
authors.forename: Richard L
authors.initials: RL
authors.lastname: Stevens
authors.forename: John
authors.initials: J
authors.lastname: Anastasi
authors.forename: Harinder
authors.initials: H
authors.lastname: Singh
mesh_terms: 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
chemical_list: 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