Although primitive yolk sac-derived erythropoiesis appears normal in these mutants, no definitive hematopoietic progenitors of any lineage are present.
Null mutations in either AML1 or CBFβ, or expression of the dominant inhibitory t(8 21)-encoded leukemia protein, AML1-ETO ( 27, 47), result in an embryonic lethal phenotype, with embryos dying during the midpoint of development from a complete absence of fetal liver-derived hematopoiesis and lethal central nervous system hemorrhages. Our laboratory ( 29) as well as those of others ( 42, 43) has demonstrated that the AML1/core binding factor β (CBFβ) transcription factor complex, the most common target of chromosomal translocations in human leukemia (reviewed in reference 23), is essential for the formation of the definitive hematopoietic system.
#Marty friedman metal clone x rar series
The development of the hematopoietic system is regulated by a series of lineage-restricted transcription factors that control critical cell fate decisions, including the formation of primitive and definitive hematopoietic stem cells from embryonic mesoderm and the survival, expansion, lineage commitment, and differentiation of more committed progenitors. These results suggest an important role for this protein in erythropoiesis. Importantly, inhibition of HERF1 expression blocked terminal erythroid differentiation of the murine erythroleukemia cell line MEL, whereas its overexpression induced erythroid maturation. Expression of HERF1 during embryogenesis coincides with the appearance of definitive erythropoiesis and in adult mice is restricted to erythroid cells, increasing 30-fold during terminal differentiation. HERF1 contains a tripartite RING finger–B box–α-helical coiled-coil domain and a C-terminal region homologous to the ret proto-oncogene-encoded finger protein. Using a differential cloning approach to define components of this pathway, we have identified a novel gene designated HERF1 (for hematopoietic RING finger 1), whose expression during development is dependent on the presence of functional AML1/CBFβ. The AML1/core binding factor β (CBFβ) transcription factor is essential for definitive hematopoiesis however, the downstream pathways through which it functions remain incompletely defined.
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