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Normal Hemopoiesis and Stemcellology

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

Leukemia volume 14, pages 863–873 (2000)Cite this article

Abstract

DNA binding by the CCAAT-displacement protein, the mammalian homologue of the Drosophila melanogaster Cut protein, was previously found to increase sharply in S phase, suggesting a role for CDP/Cut in cell cycle progression. Genetic studies in Drosophilaindicated 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 hematopoietic cell lines that can be induced to differentiate in vitro into distinct cell types. While CDP/Cut DNA binding activity declined in the pathways leading to macrophages, granulocytes and erythrocytes, it remained elevated in megakaryocytes. CDP/Cut was also highly expressed in primary megakaryocytes isolated from mouse, and some DNA binding activity could be detected. Altogether, these results raise the possibility that CDP/Cut may be a determinant of cell type identity downstream of the myelo-erythroid precursor cell. Another possibility, which does not exclude a role in lineage identity, is that CDP/Cut activity in megakaryocytes is linked to endomitosis. Indeed, elevated CDP/Cut activity in differentiating megakaryocytes and during the S phase of the cell cycle suggests that it may be required for DNA replication.

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Acknowledgements

This research was supported by grant No. MT-11590 from the Medical Research Council of Canada and No. 3497 from the National Cancer Institute of Canada to AN, grant Nos NIH R01 CA31615 and NIH R01 DK49855 to KK, and grant No. K08 HL03498 to JGD. AN is the recipient of a scholarship from the Fonds de la Recherche en Santé du Québec. NM-S is the recipient of a fellowship from the Royal Victoria Hospital Research Institute, and JGD is the recipient of an ASH Fellow Scholar Award.

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  1. JG Drachman

    Present address: Puget Sound Blood Center, University of Washington, 921 Terry Ave, Room 428B, Seattle, WA 98104, USA

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  1. Molecular Oncology Group, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada

    N Martin-Soudant & A Nepveu

  2. Division of Hematology University of Washington School of Medicine, Seattle, Washington, USA

    JG Drachman & K Kaushansky

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Martin-Soudant, N., Drachman, J., Kaushansky, K. et al. CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes. Leukemia 14, 863–873 (2000). https://doi.org/10.1038/sj.leu.2401764

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