Chromatin structure of a 3-methylcholanthrene-induced cytochrome P-450 gene.
Plasmids carrying fragments of a cytochrome P-450 gene, inducible by 3-methylcholanthrene, were used to study the chromatin structure of this gene in the liver of normal and carcinogen-treated rats. Digestion with micrococcal nuclease revealed that the gene is not present in the typical 200 base pair nucleosomal structure. By use of indirect end-label hybridization, four DNase I hypersensitive sites were mapped in the 5'-terminal region of the gene. An S1 nuclease sensitive site is located close to a DNase I site. Gene induction by treatment with 3-methylcholanthrene does not result in detectable changes in the DNase I hypersensitive sites. Rat thymus chromatin does not contain DNase I hypersensitive sites in the P-450 gene, suggesting that in the liver the chromatin structure is altered so as to allow tissue-specific expression of the gene. This paper is the first study on the chromatin structure of a gene coding for a member of the cytochrome P-450 family of enzymes. The implications of our results to the understanding of gene regulation of the P-450 genes are discussed.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D003850:Deoxyribonuclease I; D005796:Genes / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D051381:Rats; D011919:Rats, Inbred Strains
D002843:Chromatin; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D003850:Deoxyribonuclease I