Genome-wide prediction of topoisomerase IIB binding by architectural factors and chromatin accessibility

Aberrant activity of type II topoisomerases (TOP2) often causes blocked double-strand breaks (DSBs), whose inefficient repair can seriously compromise genomic stability. One of the two TOP2 paralogs encoded in vertebrates is TOP2B, which has been linked to essential processes such as transcription or genome organization. Few TOP2B genome-wide maps have been profiled, and a comprehensive study of the mechanisms involved in TOP2B-DNA binding is still lacking. Here, we conduct an in silico approach for the prediction of TOP2B binding sites using publicly available sequencing data. We achieve highly accurate predictions and find that open chromatin and architectural factors are the most informative features. We also validate our predictions on experimental data and generate predicted TOP2B tracks that mirror experimental ones with high precision.