Dynamic Reassociation of the Nuclear Lamina with Newly Replicated DNA

Abstract

The physical association of specific regions of chromatin with components of the nuclear lamina provides the framework for the 3-dimensionl architecture of the genome. The regulation of these interactions plays a critical role in the maintenance of gene expression patterns and cell identity. The breakdown and reassembly of the nuclear membrane as cells transit mitosis plays a central role in the regulation of the interactions between the genome and the nuclear lamina. However, other nuclear processes, such as transcription, have emerged as regulators of the association of DNA with the nuclear lamina. To determine whether DNA replication also has the potential to regulate DNA-nuclear lamina interactions, we adapted proximity ligation-based chromatin assembly assays to analyze the dynamics of nuclear lamina association with newly replicated DNA. We observe that lamin A/C and lamin B, as well as inner nuclear membrane proteins LBR and emerin, are found in proximity to newly replicated DNA. While core histones rapidly reassociate with DNA following passage of the replication fork, the complete reassociation of nuclear lamina components with newly replicated DNA occurs over a period of approximately 30 minutes. We propose models to describe the disassembly and reassembly of nascent chromatin with the nuclear lamina.