DNA-binding protein that induces cell differentiation

Macrophage and granulocyte-inducing (MGI) proteins regulate the growth and differentiation of myeloid hematopoietic cells. One class of these proteins (MGI-1) induces cell growth and another class (MGI-2) induces cell differentiation. Results obtained with DNA-cellulose column chromatography have shown that the differentiation-inducing protein MGI-2 can bind to double-stranded cellular DNA, but that there was no such binding under the same conditions by the growth-inducing protein MGI-1. DNA binding may thus be used to separate MGI-2 from MGI-1. The MGI-2 from mouse bound to DNA from mouse and calf. There were different elution peaks of the MGI-2 bound to DNA suggesting a heterogeneity of MGI-2 molecules, and the last peak eluted from the DNA cellulose column was enriched for one of the molecular forms of MGI-2. After one further step of purification by polyacrylamide gel electrophoresis, this molecular form of MGI-2 was active at a concentration of 6.5 X 10(-11) M. In normal development MGI-1 induces MGI-2. This induction of a DNA-binding differentiation-inducing protein by a growth-inducing protein is an efficient mechanism for the normal coupling of growth and differentiation. It is suggested that this may also be a mechanism for the normal coupling of growth and differentiation in other types of cells.