CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes

DNA binding by the CCAAT-displacement protein, the mammalian homologue of t he Drosophila melanogaster Cut protein, was previously found to increase sh arply in S phase, suggesting a role for CDP/Cut in cell cycle progression. Genetic studies in Drosophila indicated that cut plays an important role in cell-type specification in several tissues. In the present study, we have investigated CDP/Cut expression and activity in a panel of multipotent hema topoietic cell lines that can be induced to differentiate in vitro into dis tinct cell types. While CDP/Cut DNA binding activity declined in the pathwa ys leading to macrophages, granulocytes and erythrocytes, it remained eleva ted in megakaryocytes. CDP/Cut was also highly expressed in primary megakar yocytes isolated from mouse, and some DNA binding activity could be detecte d. Altogether, these results raise the possibility that CDP/Cut may be a de terminant of cell type identity downstream of the myelo-erythroid precursor cell. Another possibility, which does not exclude a role in lineage identi ty, is that CDP/Cut activity in megakaryocytes is linked to endomitosis. In deed, elevated CDP/Cut activity in differentiating megakaryocytes and durin g the S phase of the cell cycle suggests that it may be required for DNA re plication.