Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence
In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutiv...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Cold Spring Harbor Laboratory Press
2013
|
| Online Access: | http://hdl.handle.net/1721.1/80789 https://orcid.org/0000-0002-1196-5401 |
| _version_ | 1826217516738805760 |
|---|---|
| author | Meuleman, Wouter Peric-Hupkes, Daan Kind, Jop Beaudry, Jean-Bernard Pagie, Ludo Kellis, Manolis Reinders, Marcel Wessels, Lodewyk van Steensel, Bas |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Meuleman, Wouter Peric-Hupkes, Daan Kind, Jop Beaudry, Jean-Bernard Pagie, Ludo Kellis, Manolis Reinders, Marcel Wessels, Lodewyk van Steensel, Bas |
| author_sort | Meuleman, Wouter |
| collection | MIT |
| description | In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this “A/T rule” in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition. |
| first_indexed | 2024-09-23T17:04:54Z |
| format | Article |
| id | mit-1721.1/80789 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:04:54Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/807892022-09-29T23:32:05Z Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence Meuleman, Wouter Peric-Hupkes, Daan Kind, Jop Beaudry, Jean-Bernard Pagie, Ludo Kellis, Manolis Reinders, Marcel Wessels, Lodewyk van Steensel, Bas Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Meuleman, Wouter Kellis, Manolis In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this “A/T rule” in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition. 2013-09-18T14:34:27Z 2013-09-18T14:34:27Z 2012-11 2012-10 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/80789 Meuleman, W., D. Peric-Hupkes, J. Kind, J.-B. Beaudry, L. Pagie, M. Kellis, M. Reinders, L. Wessels, and B. van Steensel. “Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.” Genome Research 23, no. 2 (February 1, 2013): 270-280. https://orcid.org/0000-0002-1196-5401 en_US http://dx.doi.org/10.1101/gr.141028.112 Genome Research Creative Commons Attribution http://creativecommons.org/licenses/by-nc/3.0/ application/pdf Cold Spring Harbor Laboratory Press Genome Research |
| spellingShingle | Meuleman, Wouter Peric-Hupkes, Daan Kind, Jop Beaudry, Jean-Bernard Pagie, Ludo Kellis, Manolis Reinders, Marcel Wessels, Lodewyk van Steensel, Bas Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title | Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title_full | Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title_fullStr | Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title_full_unstemmed | Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title_short | Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence |
| title_sort | constitutive nuclear lamina genome interactions are highly conserved and associated with a t rich sequence |
| url | http://hdl.handle.net/1721.1/80789 https://orcid.org/0000-0002-1196-5401 |
| work_keys_str_mv | AT meulemanwouter constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT perichupkesdaan constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT kindjop constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT beaudryjeanbernard constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT pagieludo constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT kellismanolis constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT reindersmarcel constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT wesselslodewyk constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence AT vansteenselbas constitutivenuclearlaminagenomeinteractionsarehighlyconservedandassociatedwithatrichsequence |