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dc.contributor.authorVertii, Anastassiia
dc.contributor.authorOu, Jianhong
dc.contributor.authorYu, Jun
dc.contributor.authorYan, Aimin
dc.contributor.authorPagès, Hervé
dc.contributor.authorLiu, Haibo
dc.contributor.authorZhu, Lihua Julie
dc.contributor.authorKaufman, Paul D.
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:34Z
dc.date.available2022-08-23T15:53:34Z
dc.date.issued2018-12-03
dc.date.submitted2018-12-26
dc.identifier.citation<p>bioRxiv 484568; doi: https://doi.org/10.1101/484568. <a href="https://doi.org/10.1101/484568" target="_blank">Link to preprint on bioRxiv service.</a></p>
dc.identifier.doi10.1101/484568
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29379
dc.description.abstractIn interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery and with the nuclear lamina, and generally display characteristics of constitutive heterochromatin, including late DNA replication, enrichment of H3K9me3 and little gene expression. In contrast, Type II NADs associate with nucleoli but do not overlap with LADs. Type II NADs tend to replicate earlier, display greater gene expression, and are more often enriched in H3K27me3 than Type I NADs. The nucleolar associations of both classes of NADs were confirmed via DNA-FISH, which also detected Type I but not Type II probes enriched at the nuclear lamina. Interestingly, Type II NADs are enriched in distinct gene classes, notably factors important for differentiation and development. In keeping with this, we observed that a Type II NAD is developmentally regulated, present in MEFs but not in undifferentiated embryonic stem (ES) cells.
dc.language.isoen_US
dc.relationNow published in Genome Research doi: 10.1101/gr.247072.118
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectnucleolus associated domains
dc.subjectNADs
dc.subjectchromatin territories
dc.subjectnucleolus
dc.subjecthistone modification
dc.subjectgenomics
dc.subjectfibroblast
dc.subjectheterochromatin
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBioinformatics
dc.subjectCell Biology
dc.subjectCells
dc.subjectEmbryonic Structures
dc.subjectGenetic Phenomena
dc.subjectGenomics
dc.subjectStructural Biology
dc.titleTwo Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2618&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1608
dc.identifier.contextkey13535518
refterms.dateFOA2022-08-23T15:53:34Z
html.description.abstract<p>In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery and with the nuclear lamina, and generally display characteristics of constitutive heterochromatin, including late DNA replication, enrichment of H3K9me3 and little gene expression. In contrast, Type II NADs associate with nucleoli but do not overlap with LADs. Type II NADs tend to replicate earlier, display greater gene expression, and are more often enriched in H3K27me3 than Type I NADs. The nucleolar associations of both classes of NADs were confirmed via DNA-FISH, which also detected Type I but not Type II probes enriched at the nuclear lamina. Interestingly, Type II NADs are enriched in distinct gene classes, notably factors important for differentiation and development. In keeping with this, we observed that a Type II NAD is developmentally regulated, present in MEFs but not in undifferentiated embryonic stem (ES) cells.</p>
dc.identifier.submissionpathfaculty_pubs/1608
dc.contributor.departmentDepartment of Molecular, Cellular and Cancer Biology


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.