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 overall folding of interphase chromosomes. While LADs have been characterized in great detail, little is known about their dynamics during interphase, in particular at the onset of G1 phase and during DNA replication. To study these dynamics, 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.

Authors

Tom van Schaik  •  Mabel Vos  •  Daan Peric-Hupkes  •  Bas van Steensel

Link

https://www.biorxiv.org/content/10.1101/2019.12.19.881979v1