The chromatin structure of genes coding for P-450 enzymes is being investigated. Changes in the chromatin structure upon gene activation is examined by comparing the chromatin structure of these genes in nuclei purified from either normal or carcinogen-treated rats. Micrococcal nuclease digestion revealed that, in the liver, genes coding for the 3-methylcholanthrene-inducible P-450c, P-450d, and P-450m enzymes are not organized in the typical 200 base pair nucleosomal conformation. DNase 1 hypersensitive sites were mapped in each of these genes. These sites were not observed in nuclei isolated from the thymus. These results suggest that in the liver the chromatin structure is altered to allow tissue-specific gene expression. Gene induction by carcinogen treatment is associated with a rearrangement of the nuclear location of the P-450c and P-450d genes and with a change in one of the DNase 1 hypersensitive sites present in the P-450c gene. The results suggest that gene induction is associated with detectable changes in the chromatin structure of these genes.
