Inter-chromosomal contacts demarcate genome topology along a spatial gradient
Abstract Non-homologous chromosomal contacts (NHCCs) between different chromosomes participate considerably in gene and genome regulation. Due to analytical challenges, NHCCs are currently considered as singular, stochastic events, and their extent and fundamental principles across cell types remain...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53983-y |
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| author | Milad Mokhtaridoost Jordan J. Chalmers Marzieh Soleimanpoor Brandon J. McMurray Daniella F. Lato Son C. Nguyen Viktoria Musienko Joshua O. Nash Sergio Espeso-Gil Sameen Ahmed Kate Delfosse Jared W. L. Browning A. Rasim Barutcu Michael D. Wilson Thomas Liehr Adam Shlien Samin Aref Eric F. Joyce Anja Weise Philipp G. Maass |
| author_facet | Milad Mokhtaridoost Jordan J. Chalmers Marzieh Soleimanpoor Brandon J. McMurray Daniella F. Lato Son C. Nguyen Viktoria Musienko Joshua O. Nash Sergio Espeso-Gil Sameen Ahmed Kate Delfosse Jared W. L. Browning A. Rasim Barutcu Michael D. Wilson Thomas Liehr Adam Shlien Samin Aref Eric F. Joyce Anja Weise Philipp G. Maass |
| author_sort | Milad Mokhtaridoost |
| collection | DOAJ |
| description | Abstract Non-homologous chromosomal contacts (NHCCs) between different chromosomes participate considerably in gene and genome regulation. Due to analytical challenges, NHCCs are currently considered as singular, stochastic events, and their extent and fundamental principles across cell types remain controversial. We develop a supervised and unsupervised learning algorithm, termed Signature, to call NHCCs in Hi-C datasets to advance our understanding of genome topology. Signature reveals 40,282 NHCCs and their properties across 62 Hi-C datasets of 53 diploid human cell types. Genomic regions of NHCCs are gene-dense, highly expressed, and harbor genes for cell-specific and sex-specific functions. Extensive inter-telomeric and inter-centromeric clustering occurs across cell types [Rabl’s configuration] and 61 NHCCs are consistently found at the nuclear speckles. These constitutive ‘anchor loci’ facilitate an axis of genome activity whilst cell-type-specific NHCCs act in discrete hubs. Our results suggest that non-random chromosome positioning is supported by constitutive NHCCs that shape genome topology along an off-centered spatial gradient of genome activity. |
| format | Article |
| id | doaj-art-ac9565cd1a404b17b3b13e344b9a0a2f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ac9565cd1a404b17b3b13e344b9a0a2f2024-11-17T12:35:42ZengNature PortfolioNature Communications2041-17232024-11-0115111710.1038/s41467-024-53983-yInter-chromosomal contacts demarcate genome topology along a spatial gradientMilad Mokhtaridoost0Jordan J. Chalmers1Marzieh Soleimanpoor2Brandon J. McMurray3Daniella F. Lato4Son C. Nguyen5Viktoria Musienko6Joshua O. Nash7Sergio Espeso-Gil8Sameen Ahmed9Kate Delfosse10Jared W. L. Browning11A. Rasim Barutcu12Michael D. Wilson13Thomas Liehr14Adam Shlien15Samin Aref16Eric F. Joyce17Anja Weise18Philipp G. Maass19Genetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstitutePenn Epigenetics Institute, Perelman School of Medicine, University of PennsylvaniaJena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1Genetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteGenetics and Genome Biology Program, SickKids Research InstituteDonnelly Centre, University of TorontoGenetics and Genome Biology Program, SickKids Research InstituteJena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1Genetics and Genome Biology Program, SickKids Research InstituteDepartment of Mechanical and Industrial Engineering, University of TorontoPenn Epigenetics Institute, Perelman School of Medicine, University of PennsylvaniaJena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1Genetics and Genome Biology Program, SickKids Research InstituteAbstract Non-homologous chromosomal contacts (NHCCs) between different chromosomes participate considerably in gene and genome regulation. Due to analytical challenges, NHCCs are currently considered as singular, stochastic events, and their extent and fundamental principles across cell types remain controversial. We develop a supervised and unsupervised learning algorithm, termed Signature, to call NHCCs in Hi-C datasets to advance our understanding of genome topology. Signature reveals 40,282 NHCCs and their properties across 62 Hi-C datasets of 53 diploid human cell types. Genomic regions of NHCCs are gene-dense, highly expressed, and harbor genes for cell-specific and sex-specific functions. Extensive inter-telomeric and inter-centromeric clustering occurs across cell types [Rabl’s configuration] and 61 NHCCs are consistently found at the nuclear speckles. These constitutive ‘anchor loci’ facilitate an axis of genome activity whilst cell-type-specific NHCCs act in discrete hubs. Our results suggest that non-random chromosome positioning is supported by constitutive NHCCs that shape genome topology along an off-centered spatial gradient of genome activity.https://doi.org/10.1038/s41467-024-53983-y |
| spellingShingle | Milad Mokhtaridoost Jordan J. Chalmers Marzieh Soleimanpoor Brandon J. McMurray Daniella F. Lato Son C. Nguyen Viktoria Musienko Joshua O. Nash Sergio Espeso-Gil Sameen Ahmed Kate Delfosse Jared W. L. Browning A. Rasim Barutcu Michael D. Wilson Thomas Liehr Adam Shlien Samin Aref Eric F. Joyce Anja Weise Philipp G. Maass Inter-chromosomal contacts demarcate genome topology along a spatial gradient Nature Communications |
| title | Inter-chromosomal contacts demarcate genome topology along a spatial gradient |
| title_full | Inter-chromosomal contacts demarcate genome topology along a spatial gradient |
| title_fullStr | Inter-chromosomal contacts demarcate genome topology along a spatial gradient |
| title_full_unstemmed | Inter-chromosomal contacts demarcate genome topology along a spatial gradient |
| title_short | Inter-chromosomal contacts demarcate genome topology along a spatial gradient |
| title_sort | inter chromosomal contacts demarcate genome topology along a spatial gradient |
| url | https://doi.org/10.1038/s41467-024-53983-y |
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