title: CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes.
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 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 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.
authors.affiliation: Molecular Oncology Group, McGill University, Royal Victoria Hospital, Montreal, Quebec.
authors.forename: N
authors.initials: N
authors.lastname: Martin-Soudant
authors.forename: J G
authors.initials: JG
authors.lastname: Drachman
authors.forename: K
authors.initials: K
authors.lastname: Kaushansky
authors.forename: A
authors.initials: A
authors.lastname: Nepveu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004912:Erythrocytes / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008533:Megakaryocytes / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: C080632:CUX1 protein, human; C000624101:Cux1 protein, mouse; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C066381:ct protein, Drosophila; D013755:Tetradecanoylphorbol Acetate