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In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis.

GATA-1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. To investigate the contribution of individual domains of GATA-1 to its activity, transgenic mice expressing either an N-terminus, or an N- or C-terminal zinc finger deletion of GATA-1 (Delta NT, Delta NF or Delta CF, respectively) were generated and crossed to GATA-1 germline mutant (GATA-1.05) mice. Since the GATA-1 gene is located on the X-chromosome, male GATA-1 mutants die by embryonic day 12.5. Both Delta NF and Delta CF transgenes failed to rescue the GATA-1.05/Y pups. However, transgenic mice expressing Delta NT, but not the Delta NF protein, were able to rescue definitive hematopoiesis. In embryos, while neither the Delta CF protein nor a mutant missing both N-terminal domains (Delta NTNF) was able to support primitive erythropoiesis, the two independent Delta NT and Delta NF mutants could support primitive erythropoiesis. Thus, lineage-specific transgenic rescue of the GATA-1 mutant mouse revealed novel properties that are conferred by specific domains of GATA-1 during primitive and definitive erythropoiesis, and demonstrate that the NT and NF moieties lend complementary, but distinguishable properties to the function of GATA-1.

Pubmed ID: 11566888

Authors

  • Shimizu R
  • Takahashi S
  • Ohneda K
  • Engel JD
  • Yamamoto M

Journal

The EMBO journal

Publication Data

September 17, 2001

Associated Grants

None

Mesh Terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Erythrocytes
  • Erythroid-Specific DNA-Binding Factors
  • Erythropoiesis
  • GATA1 Transcription Factor
  • Gene Expression Regulation, Developmental
  • Hematopoietic System
  • Heme
  • Male
  • Mice
  • Mice, Transgenic
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Sequence Deletion
  • Trans-Activators
  • Transcription Factors
  • Zinc Fingers