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This genome compartmentalization has been linked to various functions, but these links are still poorly understood. Interestingly, Lamina Associated Domains (LADs) share specific heterochromatin marks, defining chromatin domains with distinct genetic and epigenetic properties. Genomic regions associating with other nuclear compartments may similarly define distinct classes of chromatin domains. One major bottleneck towards a deeper understanding of nuclear organization has been the inability to convert microscopy views of nuclear compartments into genome-wide maps that show which loci are associated with which compartment, and how the chromosomal fiber traverses between compartments. In addition, there is an urgent need for more efficient methods to dissect the mechanisms by which large genomic regions are targeted to specific nuclear compartments. Finally, there is an urgent need for high-throughput approaches that query the functional relevance of genome compartmentalization. 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Unexpectedly, active, nuclear  speckle-associated genomic regions were found near typically repressive nuclear  compartments, which is attributable to the close proximity of nuclear speckles  and nucleoli in some cell types, and association of centromeres with nuclear  speckles in human embryonic stem cells (hESCs). Our study points to a more  complex and variable nuclear genome organization than suggested by current  models, as revealed by our TSA-seq methodology.", "title": "Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable  localization of heterochromatin in different cell types.", "display_title": "Kumar P et al. 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We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic  regions near nucleoli and pericentric heterochromatin in four human cell lines.  Our study confirmed that smaller chromosomes localize closer to nucleoli but  further deconvolved this by revealing a preference for chromosome arms below  36-46 Mbp in length. We identified two lamina associated domain subsets through  their differential nuclear lamina versus nucleolar positioning in different cell  lines which showed distinctive patterns of DNA replication timing and gene  expression across all cell lines. Unexpectedly, active, nuclear  speckle-associated genomic regions were found near typically repressive nuclear  compartments, which is attributable to the close proximity of nuclear speckles  and nucleoli in some cell types, and association of centromeres with nuclear  speckles in human embryonic stem cells (hESCs). Our study points to a more  complex and variable nuclear genome organization than suggested by current  models, as revealed by our TSA-seq methodology.", "journal": "Communications biology", "uuid": "22e02dc4-37b9-4891-9084-6d85f6683252", "short_attribution": "Kumar P et al. 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