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dc.contributor.authorFinn, Elizabeth H.
dc.contributor.authorPegoraro, Gianluca
dc.contributor.authorBrandao, Hugo B.
dc.contributor.authorValton, Anne-Laure
dc.contributor.authorOomen, Marlies E.
dc.contributor.authorDekker, Job
dc.contributor.authorMirny, Leonid
dc.contributor.authorMisteli, Tom
dc.date2022-08-11T08:10:59.000
dc.date.accessioned2022-08-23T17:27:31Z
dc.date.available2022-08-23T17:27:31Z
dc.date.issued2019-03-07
dc.date.submitted2019-06-21
dc.identifier.citation<p>Cell. 2019 Mar 7;176(6):1502-1515.e10. doi: 10.1016/j.cell.2019.01.020. Epub 2019 Feb 21. <a href="https://doi.org/10.1016/j.cell.2019.01.020">Link to article on publisher's site</a></p>
dc.identifier.issn0092-8674 (Linking)
dc.identifier.doi10.1016/j.cell.2019.01.020
dc.identifier.pmid30799036
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49883
dc.description.abstractSeveral general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30799036&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.cell.2019.01.020
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectComputational Biology
dc.subjectGenetic Phenomena
dc.subjectGenomics
dc.subjectMolecular Biology
dc.subjectStructural Biology
dc.subjectSystems Biology
dc.titleExtensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization
dc.typeJournal Article
dc.source.journaltitleCell
dc.source.volume176
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/sysbio_pubs/154
dc.identifier.contextkey14784918
html.description.abstract<p>Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population.</p>
dc.identifier.submissionpathsysbio_pubs/154
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Systems Biology
dc.source.pages1502-1515.e10


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