5-bromodeoxyuridine suppresses position effect variegation of transgenes in HeLa cells

An ectopic gene integrated in the host genome is occasionally silenced due to a position effect of its adjacent chromatin structure. We found that 5-b romodeoxyuridine clearly activated such a transgene in HeLa cells. The tran sgene was also activated to various degrees by inhibitors of histone deacet ylase, DNA topoisomerases, or DNA methyltransferase. The peptide antibiotic distamycin A potentiated markedly the effect of 8-bromodeoxyuridine. Trans ient expression of an artificial AT-hook protein termed MATH20 also potenti ated its effect although significantly activated the transgene alone. Since distamycin A and MATH20 are able to displace histone H1 and other DNA-bind ing proteins bound to specific AT-rich sequences by a dominant, mutually ex clusive fashion, these results suggest that 5-bromodeoxyuridine targets suc h an AT-rich sequence located adjacent to the silenced transgene, resulting in chromatin accessibility. (C) 2001 Academic Press.