Different types of hypersensitive sites in the mouse metallothionein gene region

We have examined the chromatin structure of the metallothionein (MT) gene region in MT- S49 mouse lymphoma cells and in derivatives which express MT-I alone, MT-II alone, or both genes. In all lines, these genes are contained in a 16-kilobase pair region between two DNase I sensitive sites: one site located 5.3 kilobase pairs 5' of MT-II (the 5' gene) is present in naked DNA and retained in the chromatin of all lines; the other site located 3.1 kilobase pairs 3' of MT-I is hypersensitive. Hypersensitivity at three other sites is dependent on the expression of MT genes. Two sites 5' of MT-II disappear, and a site 3' of MT-I appears regardless of which gene is activated. The fact that these sites respond when either gene is activated suggests that the regulation of the two genes is interdependent and that the region undergoes a general change in conformation with MT activation. In addition, a single site in the 5' region of MT-II becomes hypersensitive with activation of the gene and may be related directly to expression.