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Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1.

The process through which multipotential hematopoietic cells commit to distinct lineages involves the induction of specific transcription factors. PU.1 (also known as Spi-1) and GATA-1 are transcription factors essential for the development of myeloid and erythroid lineages, respectively. Overexpression of PU.1 and GATA-1 can block differentiation in lineages in which they normally are down-regulated, indicating that not only positive but negative regulation of these factors plays a role in normal hematopoietic lineage development. Here we demonstrate that a region of the PU.1 Ets domain (the winged helix-turn-helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes. We demonstrate further that GATA inhibits binding of PU.1 to c-Jun, a critical coactivator of PU.1 transactivation of myeloid promoters. Finally, PU.1 protein can inhibit both GATA-1 and GATA-2 transactivation function. Our results suggest that interactions between PU.1 and GATA proteins play a critical role in the decision of stem cells to commit to erythroid vs. myeloid lineages.

Pubmed ID: 10411939

Authors

  • Zhang P
  • Behre G
  • Pan J
  • Iwama A
  • Wara-Aswapati N
  • Radomska HS
  • Auron PE
  • Tenen DG
  • Sun Z

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 20, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA41456
  • Agency: NCI NIH HHS, Id: CA70297
  • Agency: NCI NIH HHS, Id: CA72009
  • Agency: NCI NIH HHS, Id: R01 CA070297
  • Agency: NCI NIH HHS, Id: R01 CA070297-12
  • Agency: NCI NIH HHS, Id: R29 CA070297
  • Agency: NCI NIH HHS, Id: R29 CA070297-03

Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cercopithecus aethiops
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Gene Expression Regulation
  • Hematopoiesis
  • Humans
  • Precipitin Tests
  • Protein Binding
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-jun
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Yeasts
  • Zinc Fingers