FIGURE 6.

Primitive hematopoiesis in Dot1l-MM yolk sac. DOT1L is essential for early mammalian erythropoiesis. Absence of the DOT1L protein in the Dot1l-KO mouse leads to the lack of H3K79 methylation, which results in lethal anemia. A targeted point mutation (Asn241Ala) in the methyltransferase domain of DOT1L also causes the loss of H3K79 methylation in Dot1l-MM mice. However, the methyl mutant DOT1L protein is expressed at normal levels in these mice and allows primitive hematopoiesis to proceed. These findings suggest that a methyltransferase-independent mechanism of DOT1L is crucial for primitive erythropoiesis.