Transcriptional inhibitors affecting topoisomerase II induce changes in histone methylation patterns similar to those induced by heat shock.
The relationship between gene expression and the patterns of histone methylation in Drosophila cells has been investigated using inhibitors of transcription acting at various levels. Inhibition of ribosomal RNA synthesis and processing by 5-fluorouridine or of general RNA synthesis by camptothecin, an inhibitor of topoisomerase I, does not affect the methylation pattern of core histones. This suggests that the arrest of transcription per se is not involved in the changes in histone methylation such as those encountered in heat-shocked cells. However, ethidium bromide and novobiocin, which are known to disrupt nucleosome structure, and VM-26 (teniposide), a specific inhibitor of topoisomerase II, induce changes in histone methylation patterns which, though less severe, are similar to those observed under cellular stress. These results suggest that chromatin conformation is probably an important factor in the accessibility of histones to methyltransferases.
Desrosiers
R
R
Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Tanguay
R M
RM
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004331:Drosophila melanogaster; D004996:Ethidium / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006358:Hot Temperature; D066298:In Vitro Techniques; D008745:Methylation; D009675:Novobiocin / Q000494:pharmacology; D013713:Teniposide / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology
D006657:Histones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D003609:Dactinomycin; C001943:5-fluorouridine; D013713:Teniposide; D004996:Ethidium; D014529:Uridine; D002166:Camptothecin