biostudies-literaturevan Schaik TDeutsche ForschungsgemeinschaftEuropean UnionMedical Research CouncilDutch Research Council (NWO)Dutch Cancer SocietyEU-MUR MSCA Young Researchergkaf964https://www.ebi.ac.uk/biostudies/studies/S-EPMC12464825biostudies-literatureUnknown53(18)Lamina-associated domains (LADs) are megabase-sized genomic regions anchored to the nuclear lamina (NL). Factors controlling the interactions of the genome with the NL have largely remained elusive. Here, we identified DNA topoisomerase 2 beta (TOP2B) as a regulator of these interactions. TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in a partial loss of genomic partitioning between LADs and iLADs, suggesting that this enzyme might protect specific iLADs from interacting with the NL. TOP2B depletion affects LAD interactions with lamin B receptor (LBR) more than with lamins. LBR depletion phenocopies the effects of TOP2B depletion, despite the different positioning of the two proteins in the genome. This suggests a complementary mechanism for organizing tNucleic acids researchCoordinated control of genome-nuclear lamina interactions by topoisomerase 2B and lamin B receptor.PMC12464825838555865459694466455784893402733153-SPP 220258588800924MR/J00913X/1MSCA_000020393547839SFB 1361MC_UU_00007/13Medema RHde Wit EGilbert Nde Haas Mvan Schaik Tvan Steensel BManjon AGManzo SGMagnitov MGothe HJBuckle AJNaughton CBreda JRoukos VfalseCoordinated control of genome-nuclear lamina interactions by topoisomerase 2B and lamin B receptor.Lamina-associated domains (LADs) are megabase-sized genomic regions anchored to the nuclear lamina (NL). Factors controlling the interactions of the genome with the NL have largely remained elusive. Here, we identified DNA topoisomerase 2 beta (TOP2B) as a regulator of these interactions. TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in a partial loss of genomic partitioning between LADs and iLADs, suggesting that this enzyme might protect specific iLADs from interacting with the NL. TOP2B depletion affects LAD interactions with lamin B receptor (LBR) more than with lamins. LBR depletion phenocopies the effects of TOP2B depletion, despite the different positioning of the two proteins in the genome. This suggests a complementary mechanism for organizing t2025-01-01T00:00:00Z2025 Sep2026-06-03T21:10:12.835Z2026-05-01T03:11:00.21ZS-EPMC124648254100203010.1093/nar/gkaf964