Delayed-late activation of a myeloid defensin minimal promoter by retinoids and inflammatory mediators.
Alpha-defensin-1 gene expression in promyelocytic HL-60 cells is ('delayed-late' > or =1-2 days) activated by retinoic acid (RA), lipopolysaccharide, tumor necrosis factor-alpha and elevated levels of cAMP. Using stably integrated reporter constructs, we show that this activation is directed through a proximal and distal element within a minimal (-83/+82) def1 promoter, and is mediated by phosphorylation of the associated factors, PU.1 and D1BP, in an inducer-dependent manner. Whereas binding of PU.1 to the proximal element confers cell specificity and relays the effects of most inducers, the selectively enhancing capacity of the distal element for RA- and cAMP-dependent activation is uniquely correlated with D1BP-binding. We propose that D1BP and PU.1 are the end-points of separate pathways.
Wang
Nan
N
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Su
Qin
Q
Boeckh-Herwig
Susanne
S
Yaneva
Mariana
M
Tempst
Paul
P
D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D000242:Cyclic AMP / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012176:Retinoids / Q000494:pharmacology*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D000970:Antineoplastic Agents; D000242:Cyclic AMP; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D012176:Retinoids; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins; D000099232:Proto-Oncogene Protein Spi-1