Changes in chromatin structure and nuclear matrix association of the rat cytochrome P450 2B1/2 (CYP2B1/2) gene following induction with phenobarbital.

Treatment of rats with phenobarbital has been shown to result in an enormous increase in CYP2B1/2 mRNA levels in the liver. This study was performed in order to relate this effect of phenobarbital treatment to changes in the chromatin structure of the CYP2B1/2 gene. Phenobarbital treatment was shown to be associated with a twofold increase in DNase I sensitivity of the CYP2B1/2 gene in the liver. In addition, induction of the CYP2B1/2 gene transcription by phenobarbital resulted in a marked enrichment in the liver of CYP2B1/2 sequences in the nuclear matrix as compared to the matrix-free fraction. Control studies with the CYP1A2 gene, of which the transcriptional activity is not influenced by phenobarbital, did not show any changes in both DNase I sensitivity and matrix association upon phenobarbital treatment. Furthermore, after phenobarbital treatment, no changes in DNasel sensitivity or nuclear matrix association of the CYP2B1/2 gene were observed in the kidney. These data indicate a direct, positive correlation between the structure of the rat CYP2B1/2 gene and its activity.