Effects of TPA, bryostatin 1, and retinoic acid on PO-B, AP-1, and AP-2 DNA binding during HL-60 differentiation.
PO-B was originally characterized as a transcriptional regulatory factor of the pro-opiomelanocortin (POMC) gene; however, it has become increasingly clear that this protein may be active in tissues outside the pituitary, since it is present in diverse cell types, including differentiated HL-60 promyelocytic leukemia cells. We previously showed that PO-B DNA-binding is progressively induced during differentiation of promyelomonocytic leukemic HL-60 cells to the macrophage-like lineage (with phorbol esters). We now report that PO-B DNA-binding in HL-60 cells is similarly induced during differentiation to the granulocytic lineage (with either retinoic acid or dimethylsulfoxide). Either a genetic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects. These studies have prompted our interest in the dynamics of other transcription factor changes during HL-60 differentiation. Of these, we observed that another transcription factor (AP-1) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation, but not during granulocytic differentiation. Conversely, the DNA-binding of the transcription factor AP-2 was slightly reduced by TPA-induced HL-60 differentiation but unchanged during granulocyte differentiation. From these data, we conclude that the induction of PO-B DNA binding is a general marker of HL-60 myelomonocytic differentiation, but that qualitative aspects of the induction of additional distinct transcription factors, such as AP-1, may contribute to lineage-specific determinants of cell fate.
Davis
A F
AF
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Meighan-Mantha
R L
RL
Riegel
A T
AT
D000970:Antineoplastic Agents / Q000494:pharmacology; D054713:Bryostatins; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006098:Granulocytes; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D054713:Bryostatins; D004268:DNA-Binding Proteins; D007783:Lactones; D018942:Macrolides; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C046785:bryostatin 1; D014212:Tretinoin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide