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(2025)", "ID": "PMID:38712201", "journal": "bioRxiv : the preprint server for biology", "uuid": "f2b3b3fb-e9af-484d-abeb-fe4316ffdc1a", "abstract": "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. Whereas 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.", "authors": ["Gholamalamdari O", "van Schaik T", "Wang Y", "Kumar P", "Zhang L", "Zhang Y", "Gonzalez GAH", "Vouzas AE", "Zhao PA", "Gilbert DM", "Ma J", "van Steensel B", "Belmont AS"], "date_published": "2025-02-26", "@type": ["Publication", "Item"], "display_title": "Gholamalamdari O et al. (2025) PMID:38712201", "status": "current", "title": "Beyond A and B Compartments: how major nuclear locales define nuclear genome  organization and function.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"date_published": "2020-12-18", "ID": "PMID:33355299", "status": "current", "authors": ["Zhang L", "Zhang Y", "Chen Y", "Gholamalamdari O", "Wang Y", "Ma J", "Belmont AS"], "@id": "/publications/b3bf2d54-4ac9-4808-b44d-82c35996052f/", "abstract": "TSA-seq mapping suggests that gene distance to nuclear speckles is more deterministic and predictive of gene expression levels than gene radial positioning. Gene expression correlates inversely with distance to nuclear speckles, with chromosome regions of unusually high expression located at the apex of chromosome loops protruding from the nuclear periphery into the interior. Genomic distances to the nearest lamina-associated domain are larger for loop apexes mapping closest to nuclear speckles, suggesting the possibility of conservation of speckle-associated regions. To facilitate comparison of genome organization by TSA-seq, we reduced required cell numbers 10- to 20-fold for TSA-seq by deliberately saturating protein-labeling while preserving distance mapping by the still unsaturated DNA-labeling. Only approximately 10% of the genome shows statistically significant shifts in relative nuclear speckle distances in pair-wise comparisons between human cell lines (H1, HFF, HCT116, K562); however, these moderate shifts in nuclear speckle distances tightly correlate with changes in cell type-specific gene expression. Similarly, half of  heat shock-induced gene loci already preposition very close to nuclear speckles,  with the remaining positioned near or at intermediate distance (HSPH1) to nuclear speckles but shifting even closer with transcriptional induction. Speckle association together with chromatin decondensation correlates with expression amplification upon HSPH1 activation. Our results demonstrate a largely \"hardwired\" genome organization with specific genes moving small mean distances relative to speckles during cell differentiation or a physiological transition, suggesting an important role of nuclear speckles in gene expression regulation.", "@type": ["Publication", "Item"], "title": "TSA-seq reveals a largely conserved genome organization relative to nuclear speckles with small position changes tightly correlated with gene expression changes.", "journal": "Genome research", "display_title": "Zhang L et al. (2020) PMID:33355299", "uuid": "b3bf2d54-4ac9-4808-b44d-82c35996052f", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"date_published": "2025-02-26", "ID": "PMID:38712201", "status": "current", "authors": ["Gholamalamdari O", "van Schaik T", "Wang Y", "Kumar P", "Zhang L", "Zhang Y", "Gonzalez GAH", "Vouzas AE", "Zhao PA", "Gilbert DM", "Ma J", "van Steensel B", "Belmont AS"], "@id": "/publications/f2b3b3fb-e9af-484d-abeb-fe4316ffdc1a/", "abstract": "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. Whereas 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.", "@type": ["Publication", "Item"], "title": "Beyond A and B Compartments: how major nuclear locales define nuclear genome  organization and function.", "journal": "bioRxiv : the preprint server for biology", "display_title": "Gholamalamdari O et al. 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