TU Darmstadt / ULB / TUbiblio

The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues

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
Article, Secondary publication, Publisher's Version

WarningThere is a more recent version of this item available.

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.

Item Type: Article
Erschienen: 2024
Creators: Schmidt, Annika ; Zhang, Hui ; Schmitt, Stephanie ; Rausch, Cathia ; Popp, Oliver ; Chen, Jiaxuan ; Cmarko, Dusan ; Butter, Falk ; Dittmar, Gunnar ; Lermyte, Frederik ; Cardoso, M. Cristina
Type of entry: Secondary publication
Title: The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues
Language: English
Date: 7 May 2024
Place of Publication: Darmstadt
Year of primary publication: 11 January 2024
Place of primary publication: Basel
Publisher: MDPI
Journal or Publication Title: Cells
Volume of the journal: 13
Issue Number: 2
Collation: 29 Seiten
DOI: 10.26083/tuprints-00027235
URL / URN: https://tuprints.ulb.tu-darmstadt.de/27235
Corresponding Links:
Origin: Secondary publication DeepGreen
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.

Uncontrolled Keywords: brain, heterochromatin, immunofluorescence staining, liver, quantitative mass spectrometry, proteomics
Identification Number: Artikel-ID: 139
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-272353
Additional Information:

This article belongs to the Special Issue Nuclear Organization, Dynamics and Phase Separation in Health and Disease

Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
07 Department of Chemistry
07 Department of Chemistry > Clemens-Schöpf-Institut
Date Deposited: 07 May 2024 12:51
Last Modified: 08 May 2024 07:36
PPN:
Export:
Suche nach Titel in: TUfind oder in Google

Available Versions of this Item

Send an inquiry Send an inquiry

Options (only for editors)
Show editorial Details Show editorial Details