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.
Stroop
C J
CJ
Research Institute of Toxicology, Utrecht University, The Netherlands.
Dutmer
A A
AA
Horbach
G J
GJ
D000704:Analysis of Variance; D000818:Animals; D015139:Blotting, Southern; D002843:Chromatin / Q000378:metabolism*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis* / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D015530:Nuclear Matrix / Q000187:drug effects / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010634:Phenobarbital / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D002843:Chromatin; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; D019362:Cytochrome P-450 CYP2B1; D003850:Deoxyribonuclease I; D010634:Phenobarbital