Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contac...

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Main Authors: Kind, Jop, Pagie, Ludo, de Vries, Sandra S., Nahidiazar, Leila, Dey, Siddharth S., Bienko, Magda, Zhan, Ye, Lajoie, Bryan, de Graaf, Carolyn A., Amendola, Mario, Jalink, Kees, Dekker, Job, van Oudenaarden, Alexander, van Steensel, Bas, Fudenberg, Geoffrey, Imakaev, Maksim Viktorovich, Mirny, Leonid A
Other Authors: Massachusetts Institute of Technology. Department of Physics
Format: Article
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/112800
https://orcid.org/0000-0001-5905-6517
https://orcid.org/0000-0002-5320-2728
https://orcid.org/0000-0002-0785-5410
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author Kind, Jop
Pagie, Ludo
de Vries, Sandra S.
Nahidiazar, Leila
Dey, Siddharth S.
Bienko, Magda
Zhan, Ye
Lajoie, Bryan
de Graaf, Carolyn A.
Amendola, Mario
Jalink, Kees
Dekker, Job
van Oudenaarden, Alexander
van Steensel, Bas
Fudenberg, Geoffrey
Imakaev, Maksim Viktorovich
Mirny, Leonid A
author2 Massachusetts Institute of Technology. Department of Physics
author_facet Massachusetts Institute of Technology. Department of Physics
Kind, Jop
Pagie, Ludo
de Vries, Sandra S.
Nahidiazar, Leila
Dey, Siddharth S.
Bienko, Magda
Zhan, Ye
Lajoie, Bryan
de Graaf, Carolyn A.
Amendola, Mario
Jalink, Kees
Dekker, Job
van Oudenaarden, Alexander
van Steensel, Bas
Fudenberg, Geoffrey
Imakaev, Maksim Viktorovich
Mirny, Leonid A
author_sort Kind, Jop
collection MIT
description Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization.
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spelling mit-1721.1/1128002022-09-26T10:19:01Z Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells Kind, Jop Pagie, Ludo de Vries, Sandra S. Nahidiazar, Leila Dey, Siddharth S. Bienko, Magda Zhan, Ye Lajoie, Bryan de Graaf, Carolyn A. Amendola, Mario Jalink, Kees Dekker, Job van Oudenaarden, Alexander van Steensel, Bas Fudenberg, Geoffrey Imakaev, Maksim Viktorovich Mirny, Leonid A Massachusetts Institute of Technology. Department of Physics Fudenberg, Geoffrey Imakaev, Maksim Viktorovich Mirny, Leonid A Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization. National Institutes of Health (U.S.) (Grant R01 GM114190) National Human Genome Research Institute (U.S.) (Grant R01 HG003143) 2017-12-19T15:04:57Z 2017-12-19T15:04:57Z 2015-09 2015-06 2017-12-18T21:03:09Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/112800 Kind, Jop et al. “Genome-Wide Maps of Nuclear Lamina Interactions in Single Human Cells.” Cell 163, 1 (September 2015): 134–147 © 2015 Elsevier Inc https://orcid.org/0000-0001-5905-6517 https://orcid.org/0000-0002-5320-2728 https://orcid.org/0000-0002-0785-5410 http://dx.doi.org/10.1016/J.CELL.2015.08.040 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC
spellingShingle Kind, Jop
Pagie, Ludo
de Vries, Sandra S.
Nahidiazar, Leila
Dey, Siddharth S.
Bienko, Magda
Zhan, Ye
Lajoie, Bryan
de Graaf, Carolyn A.
Amendola, Mario
Jalink, Kees
Dekker, Job
van Oudenaarden, Alexander
van Steensel, Bas
Fudenberg, Geoffrey
Imakaev, Maksim Viktorovich
Mirny, Leonid A
Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title_full Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title_fullStr Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title_full_unstemmed Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title_short Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells
title_sort genome wide maps of nuclear lamina interactions in single human cells
url http://hdl.handle.net/1721.1/112800
https://orcid.org/0000-0001-5905-6517
https://orcid.org/0000-0002-5320-2728
https://orcid.org/0000-0002-0785-5410
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