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Cell cycle dynamics of lamina associated DNA

View ORCID ProfileTom van Schaik, Mabel Vos, Daan Peric-Hupkes, View ORCID ProfileBas van Steensel
doi: https://doi.org/10.1101/2019.12.19.881979
Tom van Schaik
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer institute, Amsterdam, the Netherlands
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Mabel Vos
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer institute, Amsterdam, the Netherlands
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Daan Peric-Hupkes
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer institute, Amsterdam, the Netherlands
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Bas van Steensel
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer institute, Amsterdam, the Netherlands
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  • ORCID record for Bas van Steensel
  • For correspondence: b.v.steensel@nki.nl
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 19, 2019.
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Cell cycle dynamics of lamina associated DNA
Tom van Schaik, Mabel Vos, Daan Peric-Hupkes, Bas van Steensel
bioRxiv 2019.12.19.881979; doi: https://doi.org/10.1101/2019.12.19.881979
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Cell cycle dynamics of lamina associated DNA
Tom van Schaik, Mabel Vos, Daan Peric-Hupkes, Bas van Steensel
bioRxiv 2019.12.19.881979; doi: https://doi.org/10.1101/2019.12.19.881979

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