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dc.contributor.authorGdula, Michal R.
dc.contributor.authorNesterova, Tatyana B.
dc.contributor.authorPintacuda, Greta
dc.contributor.authorGodwin, Jonathan
dc.contributor.authorZhan, Ye
dc.contributor.authorOzadam, Hakan
dc.contributor.authorMcClellan, Michael
dc.contributor.authorMoralli, Daniella
dc.contributor.authorKrueger, Felix
dc.contributor.authorGreen, Catherine M.
dc.contributor.authorReik, Wolf
dc.contributor.authorKriaucionis, Skirmantas
dc.contributor.authorHeard, Edith
dc.contributor.authorDekker, Job
dc.contributor.authorBrockdorff, Neil
dc.date2022-08-11T08:09:52.000
dc.date.accessioned2022-08-23T16:46:36Z
dc.date.available2022-08-23T16:46:36Z
dc.date.issued2019-01-03
dc.date.submitted2019-02-28
dc.identifier.citation<p>Nat Commun. 2019 Jan 3;10(1):30. doi: 10.1038/s41467-018-07907-2. <a href="https://doi.org/10.1038/s41467-018-07907-2">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-018-07907-2
dc.identifier.pmid30604745
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40913
dc.description.abstractThe inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation of two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 mutant cells reveals the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including A/B compartments and partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred following SmcHD1 knockout in a somatic cell model, but in this case, independent of Xi gene derepression. We conclude that SmcHD1 is a key factor in defining the unique chromosome architecture of Xi.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30604745&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© The Author(s) 2019. 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.subjectChromatin structure
dc.subjectChromosomes
dc.subjectDosage compensation
dc.subjectEpigenetic memory
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectComputational Biology
dc.subjectMolecular Biology
dc.subjectStructural Biology
dc.subjectSystems Biology
dc.titleThe non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume10
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4725&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3713
dc.identifier.contextkey13921315
refterms.dateFOA2022-08-23T16:46:36Z
html.description.abstract<p>The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation of two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 mutant cells reveals the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including A/B compartments and partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred following SmcHD1 knockout in a somatic cell model, but in this case, independent of Xi gene derepression. We conclude that SmcHD1 is a key factor in defining the unique chromosome architecture of Xi.</p>
dc.identifier.submissionpathoapubs/3713
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Systems Biology
dc.source.pages30


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© The Author(s) 2019. 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 © The Author(s) 2019. 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/.