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The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues

dc.contributor.advisor
dc.contributor.advisor
dc.contributor.advisor
dc.contributor.author Annika, Schmidt
dc.contributor.author Hui, Zhang
dc.contributor.author Stephanie, Schmitt
dc.contributor.author Cathia, Rausch
dc.contributor.author Oliver, Popp
dc.contributor.author Jiaxuan, Chen
dc.contributor.author Dusan, Cmarko
dc.contributor.author Falk, Butter
dc.contributor.author Gunnar, Dittmar
dc.contributor.author Frederik, Lermyte
dc.contributor.author M. Cristina, Cardoso
dc.date.accessioned 2023-12-09T11:15:11Z
dc.date.available 2023-12-09T11:15:11Z
dc.date.created 2023
dc.date.issued 2023-12-09
dc.description Pericentric heterochromatin (PCH) forms spatio-temporarily distinct compartments and affects chromosome organization and stability. Albeit some of its components are known, an elucidation of its proteome and how it differs between tissues in vivo is lacking. Here, we find that PCH compartments are dynamically organized in a tissue-specific manner possibly reflecting compositional differences. As mouse brain and liver exhibit very different PCH architecture, we isolated native PCH fractions from these tissues, analyzed their protein compositions using quan-titative mass spectrometry, and compared them to identify common and tissue-specific PCH pro-teins. Besides heterochromatin-enriched proteins, the PCH proteome includes RNA/transcription and membrane-related proteins, which showed lower abundance than PCH-enriched proteins. Thus, we applied a cut-off of PCH-unspecific candidates based on their abundance and validated PCH-enriched proteins. Amongst the hits, MeCP2 was classified into brain PCH-enriched pro-teins, while linker histone H1 was not. We found that H1 and MeCP2 compete to bind to PCH and regulate PCH organization in opposite ways. Altogether, our workflow of unbiased PCH iso-lation, quantitative mass spectrometry, and validation-based analysis allowed the identification of proteins that are common and tissue-specifically enriched at PCH. Further investigation of select-ed hits revealed their opposing role in heterochromatin higher order architecture in vivo. de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4050
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject brain de_DE
dc.subject heterochromatin de_DE
dc.subject immunofluorescence staining de_DE
dc.subject liver de_DE
dc.subject quantitative mass spectrometry de_DE
dc.subject proteomics de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues de_DE
dc.type Dataset de_DE
dcterms.accessRights openAccess
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tuda.history.classification Version=2020-2024;201-03 Zellbiologie
tuda.unit TUDa

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