Interactions between the genome and the nuclear lamina are multivalent and cooperative

Overview & Synopsis

Lamina-associated domains (LADs) are megabase-sized genomic regions that interact with the nuclear lamina (NL). It is not yet understood how their interacHons with the NL are encoded in their DNA. Here, we designed an efficient LAD "scrambling" approach, based on transposonmediated local hopping of loxP recombinaHon sites, to generate series of large deleHons and inversions that span LADs and flanking sequences. Mapping of NL interacHons in these rearrangements revealed that a single LAD contacts the NL through mulHple regions that act cooperaHvely or redundantly; some have more affinity for the NL than others and can pull neighbouring sequences to the NL. Genes drawn towards the NL showed oXen, but not always, reduced expression and increased H3K9me3 levels. Furthermore, neighbouring LADs can cooperaHvely interact with the NL when placed close enough to each other. These results elucidate principles that govern the posiHoning of megabase-sized genomic regions inside the cell nucleus.