Patients with mutations of the THRA gene exhibit classical features of hypothyroidism, including erythroid disorders. We previously created a mutant mouse expressing a mutated TRα1 (denoted as PV; Thra1PV/+ mouse) that faithfully reproduces the classical hypothyroidism seen in patients. Using Thra1PV/+ mice, we explored how the TRα1PV mutant acted to cause abnormalities in erythropoiesis. Thra1...

Targeted disruption of the Runx1/ AML1 gene in mice has demonstrated that it is required for the emergence of definitive hematopoietic cells but that it is not essential for the formation of primitive erythrocytes. These findings led to the conclusion that Runx1 is a stage-specific transcription factor acting only during definitive hematopoiesis. However, the zebrafish and Xenopus homologs of R...

Mammalian Krüppel-like transcription factors include 12 zinc finger proteins (KLF1-12) that are involved in regulation of cell proliferation and differentiation during morphogenesis and development (Trends Biochem. Sci., 24 (1999) 236). Structural considerations have segregated KLF6 and KLF7 into a separate sub-group, whereas in situ hybridizations have revealed predominant expression of the mo...

The Krüppel-like factors (KLFs) are a family of C2/H2 zinc finger DNA-binding proteins that are important in controlling developmental programs. Erythroid Krüppel-like factor (EKLF or KLF1) positively regulates the beta-globin gene in definitive erythroid cells. KLF2 (LKLF) is closely related to EKLF and is expressed in erythroid cells. KLF2-/- mice die between embryonic day 12.5 (E12.5) and E1...

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 ...

Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and beta-globin gene regulation but failure to rectify lethal fetal anemia upon correction of globin chain imbalance suggested additional critical EKLF target genes. We employed expression profiling of EKLF-null fetal liver and EKLF-null erythroid cell lines containing an inducible EKLF-estrogen rece...

The Krüppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Krüppel-like factor (EKLF or KLF1) regulates adult beta-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and betah1-, but not adult betaglobin, gene expression in mice. Both EKLF and KLF2 play roles in primitive...