Negative regulation of a special, double AP-1 consensus element in the vimentin promoter: interference by the retinoic acid receptor.

Abstract

The growth-regulated vimentin gene contains a functional double AP-1 binding site formed by two nearly perfect inverted repeats. We present evidence for down-regulation of vimentin expression by the retinoic acid receptor (RAR) in two mesodermally derived cell types. By mutation analysis we prove that the double consensus element is responsible for this negative regulation. From in vitro protein-DNA interaction studies we conclude that AP-1 binding is inhibited at RAR amounts required for occupation of the cognate RAR binding site in nuclear extracts from 3T3 cells and differentiated embryonal carcinoma cells. Furthermore, we show that, unlike in other cases, trans-activation of the vimentin AP-1 enhancer element can occur in undifferentiated embryonal carcinoma cells, despite the low amount of Jun and Fos proteins present in these cells. Here, however, down-regulation by retinoic acid cannot be detected.