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 fact or of the pro-opiomelanocortin (POMC) gene; however, it has become inc reasingly clear that this protein may be active in tissues outside the pituitary, since it is present in diverse cell types, including diffe rentiated HL-60 promyelocytic leukemia cells. We previously showed tha t 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 ce lls is similarly induced during differentiation to the granulocytic li neage (with either retinoic acid or dimethylsulfoxide). Either a genet ic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects. These studies have prompted our interest in the dy namics of other transcription factor changes during HL-60 differentiat ion. Of these, we observed that another transcription factor (AP-1) is also robustly induced at the DNA-binding level during macrophagelike HL-60 differentiation, but not during granulocytic differentiation. Co nversely, the DNA-binding of the transcription factor AP-2 was slightl y reduced by TPA-induced HL-60 differentiation bur unchanged during gr anulocyte differentiation. From these data, we conclude that the induc tion of PO-B DNA binding is a genera!marker of HL-60 myelomonocytic di fferentiation, but that qualitative aspects of the induction of additi onal distinct transcription factors, such as AP-1, may contribute to l ineage-specific determinants of cell fate. (C) 1997 Wiley-Liss, Inc.