Modulation of DNA binding of nuclear transcription factors with leucine-zipper motifs by particular endogenous polyamines in murine central and peripheral excitable tissues.

摘要

Transcriptional regulation is one of the most important functions of polyamines in the nucleus of eukaryotic cells. The addition of the endogenous polyamines spermine and spermidine markedly increased DNA binding activity of the transcription factor activator protein-1 (AP1) in a concentration-dependent manner at a concentration range of 50 to 500 microM in nuclear extracts of murine whole brain when determined in the absence of added MgCl(2) on gel retardation electrophoresis. Similar but less potent potentiation was seen with DNA binding of cAMP responsive element binding protein (CREB), while both polyamines were ineffective in affecting that of c-Myc irrespective of the addition of MgCl(2). Unlabeled AP1 probe was invariably more potent in competing for AP1 binding than unlabeled CREB probe in either the presence or absence of spermine and spermidine. In addition to whole brain, both polyamines significantly increased AP1 binding in retina, adrenal and pituitary, without significantly affecting that in spleen. Moreover, ultraviolet and circular dichroism spectra analyses revealed that these two polyamines induced DNA topological transition of AP1 probe under the conditions favorable for the increase in AP1 binding. These results suggest that both spermine and spermidine may modulate gene transcription through cis- and trans-actions on AP1 binding in the nucleus in murine central and peripheral structures with high excitability.