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Local rewiring of genome - nuclear lamina interactions by transcription

Laura Brueckner, Peiyao A Zhao, Tom van Schaik, Christ Leemans, Jiao Sima, Daniel Peric-Hupkes, View ORCID ProfileDavid M Gilbert, Bas van Steensel
doi: https://doi.org/10.1101/685255
Laura Brueckner
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
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Peiyao A Zhao
2Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA
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Tom van Schaik
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
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Christ Leemans
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
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Jiao Sima
2Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA
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Daniel Peric-Hupkes
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
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David M Gilbert
2Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA
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  • ORCID record for David M Gilbert
Bas van Steensel
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
3Department of Cell Biology, Erasmus University Medical Center, Rotterdam, the Netherlands
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  • For correspondence: b.v.steensel@nki.nl
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Abstract

Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation of such genes is often accompanied by repositioning towards the nuclear interior. How this process works and how it impacts flanking chromosomal regions is poorly understood. We addressed these questions by systematic manipulation of gene activity and detailed analysis of NL interactions. Activation of genes inside LADs typically causes detachment of the entire transcription unit but rarely more than 50-100 kb of flanking DNA, even when multiple neighboring genes are activated. The degree of detachment depends on the expression level and the length of the activated gene. Loss of NL interactions coincides with a switch from late to early replication timing, but the latter can involve longer stretches of DNA. These findings show how NL interactions can be shaped locally by transcription and point to a remarkable flexibility of interphase chromosomes.

Footnotes

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133275

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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-ND 4.0 International license.
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Posted June 27, 2019.
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Local rewiring of genome - nuclear lamina interactions by transcription
Laura Brueckner, Peiyao A Zhao, Tom van Schaik, Christ Leemans, Jiao Sima, Daniel Peric-Hupkes, David M Gilbert, Bas van Steensel
bioRxiv 685255; doi: https://doi.org/10.1101/685255
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Local rewiring of genome - nuclear lamina interactions by transcription
Laura Brueckner, Peiyao A Zhao, Tom van Schaik, Christ Leemans, Jiao Sima, Daniel Peric-Hupkes, David M Gilbert, Bas van Steensel
bioRxiv 685255; doi: https://doi.org/10.1101/685255

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