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dc.contributor.authorOudelaar, A. Marieke
dc.contributor.authorHidalgo, Daniel
dc.contributor.authorSocolovsky, Merav
dc.contributor.authorHiggs, Douglas R.
dc.contributor.authorHughes, Jim R.
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:36Z
dc.date.available2022-08-23T16:49:36Z
dc.date.issued2020-06-01
dc.date.submitted2020-07-09
dc.identifier.citation<p>Oudelaar AM, Beagrie RA, Gosden M, de Ornellas S, Georgiades E, Kerry J, Hidalgo D, Carrelha J, Shivalingam A, El-Sagheer AH, Telenius JM, Brown T, Buckle VJ, Socolovsky M, Higgs DR, Hughes JR. Dynamics of the 4D genome during in vivo lineage specification and differentiation. Nat Commun. 2020 Jun 1;11(1):2722. doi: 10.1038/s41467-020-16598-7. PMID: 32483172; PMCID: PMC7264236. <a href="https://doi.org/10.1038/s41467-020-16598-7">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-020-16598-7
dc.identifier.pmid32483172
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41495
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractMammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32483172&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGene regulation
dc.subjectNuclear organization
dc.subjectBioinformatics
dc.subjectBiophysics
dc.subjectDevelopmental Biology
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectStructural Biology
dc.titleDynamics of the 4D genome during in vivo lineage specification and differentiation
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume11
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5301&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4275
dc.identifier.contextkey18456793
refterms.dateFOA2022-08-23T16:49:36Z
html.description.abstract<p>Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.</p>
dc.identifier.submissionpathoapubs/4275
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.source.pages2722


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Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.