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dc.contributor.authorSpracklin, George
dc.contributor.authorAbdennur, Nezar
dc.contributor.authorImakaev, Maxim
dc.contributor.authorChowdhury, Neil
dc.contributor.authorPradhan, Sriharsa
dc.contributor.authorMirny, Leonid A
dc.contributor.authorDekker, Job
dc.date.accessioned2023-12-15T16:51:42Z
dc.date.available2023-12-15T16:51:42Z
dc.date.issued2022-12-22
dc.identifier.citationSpracklin G, Abdennur N, Imakaev M, Chowdhury N, Pradhan S, Mirny LA, Dekker J. Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers. Nat Struct Mol Biol. 2023 Jan;30(1):38-51. doi: 10.1038/s41594-022-00892-7. Epub 2022 Dec 22. PMID: 36550219; PMCID: PMC9851908.en_US
dc.identifier.eissn1545-9985
dc.identifier.doi10.1038/s41594-022-00892-7en_US
dc.identifier.pmid36550219
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52871
dc.description.abstractThe relationships between chromosomal compartmentalization, chromatin state and function are poorly understood. Here by profiling long-range contact frequencies in HCT116 colon cancer cells, we distinguish three silent chromatin states, comprising two types of heterochromatin and a state enriched for H3K9me2 and H2A.Z that exhibits neutral three-dimensional interaction preferences and which, to our knowledge, has not previously been characterized. We find that heterochromatin marked by H3K9me3, HP1α and HP1β correlates with strong compartmentalization. We demonstrate that disruption of DNA methyltransferase activity greatly remodels genome compartmentalization whereby domains lose H3K9me3-HP1α/β binding and acquire the neutrally interacting state while retaining late replication timing. Furthermore, we show that H3K9me3-HP1α/β heterochromatin is permissive to loop extrusion by cohesin but refractory to CTCF binding. Together, our work reveals a dynamic structural and organizational diversity of the silent portion of the genome and establishes connections between the regulation of chromatin state and chromosome organization, including an interplay between DNA methylation, compartmentalization and loop extrusion.en_US
dc.language.isoenen_US
dc.relation.ispartofNature Structural & Molecular Biologyen_US
dc.relation.urlhttps://doi.org/10.1038/s41594-022-00892-7en_US
dc.rightsOpen 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/. © The Author(s) 2022en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBiophysicsen_US
dc.subjectComputational biology and bioinformaticsen_US
dc.subjectEpigenomicsen_US
dc.subjectNuclear organizationen_US
dc.subjectSystems biologyen_US
dc.titleDiverse silent chromatin states modulate genome compartmentalization and loop extrusion barriersen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNature structural & molecular biology
dc.source.volume30
dc.source.issue1
dc.source.beginpage38
dc.source.endpage51
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalNature structural & molecular biology
refterms.dateFOA2023-12-15T16:51:46Z
dc.contributor.departmentProgram in Bioinformatics and Integrative Biologyen_US
dc.contributor.departmentSystems Biologyen_US


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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/.
© The Author(s) 2022
Except where otherwise noted, this item's license is described as 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/. © The Author(s) 2022