Delayed-late activation of a myeloid defensin minimal promoter by retinoids and inflammatory mediators

Abstract 

α-Defensin-1 gene expression in promyelocytic HL-60 cells is (‘delayed-late’ ≥1–2 days) activated by retinoic acid (RA), lipopolysaccharide, tumor necrosis factor-α 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.

Keywords:  Defensin, Granulocytes, Transcription, Phosphorylation, Retinoic acid, cAMP