TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells.

DNA topoisomerase II beta (TOP2B) is required for correct execution of certain developmental transcriptional programs and for signal-induced transcriptional activation, including transcriptional activation by nuclear hormone ligands such as retinoic acid. In addition, TOP2B is enriched at genomic locations occupied by CCCTC-Binding factor (CTCF) and cohesin (RAD21). suggesting a role in chromosome looping and/or establishing or maintaining aspects of chromosome 3D structure. This led us to investigate the effect of TOP2B inactivation on patterns of intra- and inter- chromosomal interaction that reflect the 3D architecture of the genome. Using the retinoic acid responsive SH-SY5Y neuroblastoma cell line model, we had previously demonstrated many gene expression changes upon retinoic acid treatment and upon deletion of TOP2B. We report here that these expression changes in TOP2B null versus WT cells are accompanied by surprisingly subtle changes in local chromosome organization. However, we do observe quantitative changes in chromosome organization on a megabase scale. First, lack of TOP2B did affect compartment strength changes that occur upon ATRA treatment. Second, we observe an excess of very long-range interactions, reminiscent of interactions seen in mitotic cells, suggesting the possibility that in the absence of TOP2B some mitotic interactions are retained. Third, we see quantitative changes in centromere-telomere interactions, again indicating global changes at the megabase and chromosome level. These data support the surprising conclusion that TOP2B has only a minor role in chromosome dynamics and organization.