Antibiotics induce overexpression of alpha satellite DNA accompanied with epigenetic changes at alpha satellite arrays as well as genome-wide

The transcription of satellite DNA is highly sensitive to environmental factors and represents a source of genomic instability. Therefore, tight regulation of (peri)centromeric transcription is essential for genome maintenance. Antibiotics are routinely used for in vitro studies and for medical treatment, however, their effect on pericentromeric satellite DNA transcription was not investigated. Here we show that antibiotics geneticin and hygromycin B, conveniently used in cell culture, as well as rifampicin (along with five other antibiotics), used to treat bacterial infections, increase transcription of a major human pericentromeric alpha satellite DNA in cell lines at standard concentrations. However, response differs among cell lines - maximal increase in A-1235 cells is obtained by rifampicin while in HeLa cells and fibroblasts by geneticin. There is also a positive correlation between antibiotic concentration and the level of alpha satellite transcription. The increase of transcription is accompanied with either H3K9me3 decrease or H3K18ac increase at tandemly arranged alpha satellite arrays while H3K4me2 remains unchanged. Our results suggest that induced alpha satellite DNA transcription upon antibiotic stress could be linked to epigenetic changes - histone modifications H3K9me3 and H3K18ac, which are associated with transcription of heterochromatin.