Major nuclear locales define nuclear genome organization and function beyond A and B compartments
Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nu...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/99116 |
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| author | Omid Gholamalamdari Tom van Schaik Yuchuan Wang Pradeep Kumar Liguo Zhang Yang Zhang Gabriela A Hernandez Gonzalez Athanasios E Vouzas Peiyao A Zhao David M Gilbert Jian Ma Bas van Steensel Andrew S Belmont |
| author_facet | Omid Gholamalamdari Tom van Schaik Yuchuan Wang Pradeep Kumar Liguo Zhang Yang Zhang Gabriela A Hernandez Gonzalez Athanasios E Vouzas Peiyao A Zhao David M Gilbert Jian Ma Bas van Steensel Andrew S Belmont |
| author_sort | Omid Gholamalamdari |
| collection | DOAJ |
| description | Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome. |
| format | Article |
| id | doaj-art-961722c7ccf04c76a9619058152c2e83 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-961722c7ccf04c76a9619058152c2e832025-08-20T03:13:48ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.99116Major nuclear locales define nuclear genome organization and function beyond A and B compartmentsOmid Gholamalamdari0https://orcid.org/0000-0002-5773-1205Tom van Schaik1Yuchuan Wang2Pradeep Kumar3https://orcid.org/0000-0002-1060-1286Liguo Zhang4Yang Zhang5Gabriela A Hernandez Gonzalez6Athanasios E Vouzas7Peiyao A Zhao8David M Gilbert9Jian Ma10https://orcid.org/0000-0002-4202-5834Bas van Steensel11https://orcid.org/0000-0002-0284-0404Andrew S Belmont12https://orcid.org/0000-0002-6540-0801Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesDivision of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, NetherlandsRay and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United StatesDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesRay and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United StatesDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesSan Diego Biomedical Research Institute, San Diego, United StatesSan Diego Biomedical Research Institute, San Diego, United StatesSan Diego Biomedical Research Institute, San Diego, United StatesRay and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United StatesDivision of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, United States; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, United StatesModels of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.https://elifesciences.org/articles/99116genome organizationnuclear structurenuclear laminanuclear specklesnucleoli |
| spellingShingle | Omid Gholamalamdari Tom van Schaik Yuchuan Wang Pradeep Kumar Liguo Zhang Yang Zhang Gabriela A Hernandez Gonzalez Athanasios E Vouzas Peiyao A Zhao David M Gilbert Jian Ma Bas van Steensel Andrew S Belmont Major nuclear locales define nuclear genome organization and function beyond A and B compartments eLife genome organization nuclear structure nuclear lamina nuclear speckles nucleoli |
| title | Major nuclear locales define nuclear genome organization and function beyond A and B compartments |
| title_full | Major nuclear locales define nuclear genome organization and function beyond A and B compartments |
| title_fullStr | Major nuclear locales define nuclear genome organization and function beyond A and B compartments |
| title_full_unstemmed | Major nuclear locales define nuclear genome organization and function beyond A and B compartments |
| title_short | Major nuclear locales define nuclear genome organization and function beyond A and B compartments |
| title_sort | major nuclear locales define nuclear genome organization and function beyond a and b compartments |
| topic | genome organization nuclear structure nuclear lamina nuclear speckles nucleoli |
| url | https://elifesciences.org/articles/99116 |
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