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-bromodeoxyuridine clearly activated such a transgene in HeLa cells. The transgene was also activated to various degrees by inhibitors of histone deacetylase, DNA topoisomerases, or DNA methyltransferase. The peptide antibiotic distamycin A potentiated markedly the effect of 5-bromodeoxyuridine. Transient expression of an artificial AT-hook protein termed MATH20 also potentiated its effect although significantly activated the transgene alone. Since distamycin A and MATH20 are able to displace histone H1 and other DNA-binding proteins bound to specific AT-rich sequences by a dominant, mutually exclusive fashion, these results suggest that 5-bromodeoxyuridine targets such an AT-rich sequence located adjacent to the silenced transgene, resulting in chromatin accessibility.