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 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 higher-level 3D architecture of the genome. Using the retinoic acid responsive SH-SY5Y neuroblastoma cell line model, we had previously demonstrated a large number of gene expression changes upon retinoic acid treatment and upon depletion of TOP2B. However, we report here that these expression changes are accompanied by only subtle changes in chromosome organization. While there was no evidence for changes in cohesin loops or topologically associating domains, lack of TOP2B did affect compartment strength changes that occur upon ATRA treatment. Overall design: Hi-C experiments in SH-SY5Y cell line before and after 5 days of ATRA induced differentiation, with or without TOP2B KO, 2 replicates of each condition.