Cell cycle dynamics of lamina‐associated DNA

Abstract

In mammalian interphase nuclei, more than one thousand large genomic regions are positioned at the nuclear lamina (NL). These lamina‐associated domains (LADs) are involved in gene regulation and may provide a backbone for the folding of interphase chromosomes. Little is known about the dynamics of LADs during interphase, in particular at the onset of G1 phase and during DNA replication. We developed an antibody‐based variant of the DamID technology (named pA‐DamID) that allows us to map and visualize genome–NL interactions with high temporal resolution. Application of pA‐DamID combined with synchronization and cell sorting experiments reveals that LAD–NL contacts are generally rapidly established early in G1 phase. However, LADs on the distal ~25 Mb of most chromosomes tend to contact the NL first and then gradually detach, while centromere‐proximal LADs accumulate gradually at the NL. Furthermore, our data indicate that S‐phase chromatin shows transiently increased lamin interactions. These findings highlight a dynamic choreography of LAD–NL contacts during interphase progression and illustrate the usefulness of pA‐DamID to study the dynamics of genome compartmentalization. pA‐DamID generates “snapshots” of protein – genome interactions by microscopy and by genome‐wide mapping. It here reveals the dynamics of chromosome positioning relative to the nuclear lamina during the cell cycle. pA‐DamID generates “snapshots” of protein – genome interactions by microscopy and by genome‐wide mapping. It here reveals the dynamics of chromosome positioning relative to the nuclear lamina during the cell cycle.