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ZFIN ID: ZDB-PUB-070827-15
A global role for zebrafish klf4 in embryonic erythropoiesis
Gardiner, M.R., Gongora, M.M., Grimmond, S.M., and Perkins, A.C.
Date: 2007
Source: Mechanisms of Development   124(9-10): 762-774 (Journal)
Registered Authors: Perkins, Andrew
Keywords: Kruppel-like factor, Erythropoiesis, Globin, Heme, Zebrafish
MeSH Terms:
  • Animals
  • Erythropoiesis/physiology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/physiology
  • Globins/biosynthesis
  • Globins/genetics
  • Heme/biosynthesis
  • Kruppel-Like Transcription Factors/blood
  • Kruppel-Like Transcription Factors/physiology*
  • Zebrafish/embryology*
  • Zebrafish/physiology
  • Zebrafish Proteins/blood
  • Zebrafish Proteins/physiology*
PubMed: 17709232 Full text @ Mech. Dev.
There are two waves of erythropoiesis, known as primitive and definitive waves in mammals and lower vertebrates including zebrafish. The founding member of the Kruppel-like factor (KLF) family of CACCC-box binding proteins, EKLF/Klf1, is essential for definitive erythropoiesis in mammals but only plays a minor role in primitive erythropoiesis. Morpholino knockdown experiments have shown a role for zebrafish klf4 in primitive erythropoiesis and hatching gland formation. In order to generate a global understanding of how klf4 might influence gene expression and differentiation, we have performed expression profiling of klf4 morphants, and then performed validation of many putative target genes by qRT-PCR and whole mount in situ hybridization. We found a critical role for klf4 in embryonic globin, heme synthesis and hatching gland gene expression. In contrast, there was an increase in expression of definitive hematopoietic specific genes such as larval globin genes, runx1 and c-myb from 24hpf, suggesting a selective role for klf4 in primitive rather than definitive erythropoiesis. In addition, we show klf4 preferentially binds CACCC box elements in the primitive zebrafish beta-like globin gene promoters. These results have global implications for primitive erythroid gene regulation by KLF-CACCC box interactions.