Schmidt, Annika ; Zhang, Hui ; Schmitt, Stephanie ; Rausch, Cathia ; Popp, Oliver ; Chen, Jiaxuan ; Cmarko, Dusan ; Butter, Falk ; Dittmar, Gunnar ; Lermyte, Frederik ; Cardoso, M. Cristina (2024)
The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues.
In: Cells, 2024, 13 (2)
doi: 10.26083/tuprints-00027235
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
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 the mouse brain and liver exhibit very different PCH architecture, we isolated native PCH fractions from these tissues, analyzed their protein compositions using quantitative mass spectrometry, and compared them to identify common and tissue-specific PCH proteins. In addition to 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 proteins, 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 isolation, quantitative mass spectrometry, and validation-based analysis allowed the identification of proteins that are common and tissue-specifically enriched at PCH. Further investigation of selected hits revealed their opposing role in heterochromatin higher-order architecture in vivo.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Schmidt, Annika ; Zhang, Hui ; Schmitt, Stephanie ; Rausch, Cathia ; Popp, Oliver ; Chen, Jiaxuan ; Cmarko, Dusan ; Butter, Falk ; Dittmar, Gunnar ; Lermyte, Frederik ; Cardoso, M. Cristina |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues |
| Sprache: | Englisch |
| Publikationsjahr: | 7 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 11 Januar 2024 |
| Ort der Erstveröffentlichung: | Basel |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Cells |
| Jahrgang/Volume einer Zeitschrift: | 13 |
| (Heft-)Nummer: | 2 |
| Kollation: | 29 Seiten |
| DOI: | 10.26083/tuprints-00027235 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27235 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | 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 the mouse brain and liver exhibit very different PCH architecture, we isolated native PCH fractions from these tissues, analyzed their protein compositions using quantitative mass spectrometry, and compared them to identify common and tissue-specific PCH proteins. In addition to 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 proteins, 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 isolation, quantitative mass spectrometry, and validation-based analysis allowed the identification of proteins that are common and tissue-specifically enriched at PCH. Further investigation of selected hits revealed their opposing role in heterochromatin higher-order architecture in vivo. |
| Freie Schlagworte: | brain, heterochromatin, immunofluorescence staining, liver, quantitative mass spectrometry, proteomics |
| ID-Nummer: | Artikel-ID: 139 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-272353 |
| Zusätzliche Informationen: | This article belongs to the Special Issue Nuclear Organization, Dynamics and Phase Separation in Health and Disease |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Cell Biology and Epigenetics 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 07 Mai 2024 12:51 |
| Letzte Änderung: | 08 Mai 2024 07:36 |
| PPN: | |
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| Suche nach Titel in: | TUfind oder in Google |
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- The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues. (deposited 07 Mai 2024 12:51) [Gegenwärtig angezeigt]
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