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dc.contributor.authorSpracklin, George
dc.contributor.authorAbdennur, Nezar Alexander
dc.contributor.authorImakaev, Maxim
dc.contributor.authorChowdhury, Neil
dc.contributor.authorPradhan, Sriharsa
dc.contributor.authorMirny, Leonid A
dc.contributor.authorDekker, Job
dc.date.accessioned2023-04-11T20:15:33Z
dc.date.available2023-04-11T20:15:33Z
dc.date.issued2023-01
dc.identifier.urihttps://hdl.handle.net/1721.1/150484
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>The 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.</jats:p>en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1038/s41594-022-00892-7en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNatureen_US
dc.titleDiverse silent chromatin states modulate genome compartmentalization and loop extrusion barriersen_US
dc.typeArticleen_US
dc.identifier.citationSpracklin, George, Abdennur, Nezar, Imakaev, Maxim, Chowdhury, Neil, Pradhan, Sriharsa et al. 2023. "Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers." Nature Structural &amp; Molecular Biology, 30 (1).
dc.contributor.departmentHarvard-MIT Program in Health Sciences and Technologyen_US
dc.relation.journalNature Structural &amp; Molecular Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-04-11T19:58:26Z
dspace.orderedauthorsSpracklin, G; Abdennur, N; Imakaev, M; Chowdhury, N; Pradhan, S; Mirny, LA; Dekker, Jen_US
dspace.date.submission2023-04-11T19:58:34Z
mit.journal.volume30en_US
mit.journal.issue1en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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