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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 RIS Download

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

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Associated grants

  • Agency: NCI NIH HHS, Id: CA70297
  • Agency: NCI NIH HHS, Id: R01 CA070297
  • Agency: NCI NIH HHS, Id: CA72009
  • Agency: NCI NIH HHS, Id: P01 CA072009
  • Agency: NCI NIH HHS, Id: CA41456
  • Agency: NCI NIH HHS, Id: R29 CA070297
  • Agency: NCI NIH HHS, Id: R29 CA070297-03
  • Agency: NCI NIH HHS, Id: R01 CA041456
  • Agency: NCI NIH HHS, Id: R01 CA070297-12

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