Coordinated control of genome-nuclear lamina interactions by Topoisomerase 2B and Lamin B receptor (RNA-Seq)

Lamina-associated domains (LADs) are megabase-sized portions of the genome anchored to the nuclear lamina (NL). Factors controlling the tethering of the genome to the NL have remained elusive. Here, we identified DNA Topoisomerase 2 beta (TOP2B) as a prominent regulator of genome-NL interactions. TOP2B depletion leads to the weakening of these interactions in LADs marked by H3K9me3 heterochromatin, and the repositioning of inter-LAD regions (iLADs) to the NL. TOP2B loss affects LAD interactions with Lamin B receptor (LBR) more prominently than with Lamins B1 and B2. LBR loss phenocopies the effects of TOP2B depletion, although the two proteins occupy different portions of the genome. Co-depletion of TOP2B and LBR causes partial LAD/iLADs inversion, mirroring changes typical of oncogene-induced senescence. We propose that a coordinated axis controlled by TOP2B in iLADs and LBR in LADs maintain proper partitioning of the genome between the NL and the nuclear interior. Overall design: RNA-seq experiment were performed on RPE1SunTag control and depleted for TOP2B. RNA was extracted 5 days post transfection.