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Local rewiring of genome–nuclear lamina interactions by transcription

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 toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are...

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Autores principales: Brueckner, Laura, Zhao, Peiyao A, van Schaik, Tom, Leemans, Christ, Sima, Jiao, Peric‐Hupkes, Daniel, Gilbert, David M, van Steensel, Bas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073462/
https://www.ncbi.nlm.nih.gov/pubmed/32080885
http://dx.doi.org/10.15252/embj.2019103159
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author Brueckner, Laura
Zhao, Peiyao A
van Schaik, Tom
Leemans, Christ
Sima, Jiao
Peric‐Hupkes, Daniel
Gilbert, David M
van Steensel, Bas
author_facet Brueckner, Laura
Zhao, Peiyao A
van Schaik, Tom
Leemans, Christ
Sima, Jiao
Peric‐Hupkes, Daniel
Gilbert, David M
van Steensel, Bas
author_sort Brueckner, Laura
collection PubMed
description 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 toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are poorly understood. We addressed these questions by systematic activation or inactivation of individual genes, followed by detailed genome‐wide analysis of NL interactions, replication timing, and transcription patterns. Gene activation inside LADs typically causes NL 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. Inactivation of active genes can lead to increased NL contacts. These extensive datasets are a resource for the analysis of LAD rewiring by transcription and reveal a remarkable flexibility of interphase chromosomes.
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spelling pubmed-70734622020-03-18 Local rewiring of genome–nuclear lamina interactions by transcription Brueckner, Laura Zhao, Peiyao A van Schaik, Tom Leemans, Christ Sima, Jiao Peric‐Hupkes, Daniel Gilbert, David M van Steensel, Bas EMBO J Articles 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 toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are poorly understood. We addressed these questions by systematic activation or inactivation of individual genes, followed by detailed genome‐wide analysis of NL interactions, replication timing, and transcription patterns. Gene activation inside LADs typically causes NL 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. Inactivation of active genes can lead to increased NL contacts. These extensive datasets are a resource for the analysis of LAD rewiring by transcription and reveal a remarkable flexibility of interphase chromosomes. John Wiley and Sons Inc. 2020-02-21 2020-03-16 /pmc/articles/PMC7073462/ /pubmed/32080885 http://dx.doi.org/10.15252/embj.2019103159 Text en © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Brueckner, Laura
Zhao, Peiyao A
van Schaik, Tom
Leemans, Christ
Sima, Jiao
Peric‐Hupkes, Daniel
Gilbert, David M
van Steensel, Bas
Local rewiring of genome–nuclear lamina interactions by transcription
title Local rewiring of genome–nuclear lamina interactions by transcription
title_full Local rewiring of genome–nuclear lamina interactions by transcription
title_fullStr Local rewiring of genome–nuclear lamina interactions by transcription
title_full_unstemmed Local rewiring of genome–nuclear lamina interactions by transcription
title_short Local rewiring of genome–nuclear lamina interactions by transcription
title_sort local rewiring of genome–nuclear lamina interactions by transcription
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073462/
https://www.ncbi.nlm.nih.gov/pubmed/32080885
http://dx.doi.org/10.15252/embj.2019103159
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