Model of hematopoietic lineage switching.

The scheme is based on the reciprocal lineage switches between MEP cells and myeloblasts induced by GATA-1 and PU.1 (see text). The left part of the figure illustrates that the balance between the 2 factors determines the cell's phenotype; MEPs are specified by an excess of GATA-1, myeloblasts by an excess of PU.1. The right part of the figure illustrates what might be going on in the nucleus. In MEP cells GATA-1 activates multiple target genes (A, B, C), as well as possiblyGATA-1 itself. In myeloid cells PU.1 activates another set of target genes (X, Y, Z), including PU.1 itself. Enforced expression of PU.1 in MEP cells leads to the inactivation of GATA-1 through direct protein interactions. GATA-1, when overexpressed in myeloid cells, inactivates PU.1 through a similar mechanism (the cross-antagonism between the 2 factors is illustrated by the T bars).