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Metal-Responsive Elements act as Positive Modulators of Human Metallothionein-II A Enhancer Activity

1987; Taylor & Francis; Volume: 7; Issue: 2 Linguagem: Inglês

10.1128/mcb.7.2.606-613.1987

1098-5549

Michael Karin, Alois Haslinger, Adriana Heguy, Therese A. Dietlin, Tracy Cooke,

Plant Micronutrient Interactions and Effects

The human metallothionein IIA (hMT-IIA) gene contains two enhancer elements whose activity is induced by heavy-metal ions such as Cd2+. To determine the nature of the relationship between the metal-responsive elements and the element(s) responsible for the basal activity of the enhancers, the basal-level enhancer element(s), the hMT-IIA enhancers were subjected to mutational analysis. We show that deletion of the metal-responsive elements had no effect on the basal activity of the enhancer but prevented further induction by Cd2+. On the other hand, replacement of the basal-level enhancer element with linker DNA led to inactivation of the enhancer both before and after treatment with Cd2+. Therefore, the metal-responsive elements seems to act as a positive modulator of enhancer function in the presence of heavy-metal ions. In addition to the two enhancers, the hMT-IIA promoter contained one other element, the GC box, required for its basal expression. Unlike deletion of the basal-level enhancer element, replacement of the GC box with linker DNA had no effect on the ability of the promoter to be induced by Cd2+.