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.

Nuclear blebs are associated with destabilized chromatin packing domains

“…Recently, proximity ligation-based chromatin assembly assays have been applied to investigate the kinetics of nuclear lamina binding to newly replicated DNA in mouse embryonic fibroblasts. [51] Finally, computational models have been applied to probe the time evolution of the chromatin over the G1 phase of the interphase in Drosophilla that successfully predict dynamic positioning of all LADs at the nuclear envelope. [52] While Chromatin Scanning Transmission Electron Microscopy (ChromSTEM) does not have live-cell imaging capabilities to resolve chromatin mobility [29], future work may involve this high-resolution imaging technique to investigate how the shift in chromatin dynamics seen here could be related to shifts in chromatin density, volume, and shape.…”

Epigenetic determinants of fusion-driven sarcomas: paradigms and challenges

“…Thus, there is incredible potential to make a vast impact through understanding how an epigenetic state is heritable in a sarcoma cell, in a bulk cell context, or more excitingly, within discrete populations in single cells. Key studies in developmental systems in this area have been pioneered in recent years in the context of nascent histone acetylation ( Popova et al, 2021 ; Lovejoy et al, 2023 ) and nucleosome turnover ( Flury et al, 2023 ; Wenger et al, 2023 ), along with exciting innovative methodologies to map chromatin dynamics in newly replicated chromatin ( Petryk et al, 2021 ; Stewart-Morgan and Groth, 2023 ). What key advances can be made through combining these high impact technologies with central questions in cell cycle epigenetics in sarcoma?…”