Specificity, propagation, and memory of pericentric heterochromatin
Abstract The cell establishes heritable patterns of active and silenced chromatin via interacting factors that set, remove, and read epigenetic marks. To understand how the underlying networks operate, we have dissected transcriptional silencing in pericentric heterochromatin (PCH) of mouse fibrobla...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2014-08-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20145377 |
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| _version_ | 1849234336609468416 |
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| author | Katharina Müller‐Ott Fabian Erdel Anna Matveeva Jan‐Philipp Mallm Anne Rademacher Matthias Hahn Caroline Bauer Qin Zhang Sabine Kaltofen Gunnar Schotta Thomas Höfer Karsten Rippe |
| author_facet | Katharina Müller‐Ott Fabian Erdel Anna Matveeva Jan‐Philipp Mallm Anne Rademacher Matthias Hahn Caroline Bauer Qin Zhang Sabine Kaltofen Gunnar Schotta Thomas Höfer Karsten Rippe |
| author_sort | Katharina Müller‐Ott |
| collection | DOAJ |
| description | Abstract The cell establishes heritable patterns of active and silenced chromatin via interacting factors that set, remove, and read epigenetic marks. To understand how the underlying networks operate, we have dissected transcriptional silencing in pericentric heterochromatin (PCH) of mouse fibroblasts. We assembled a quantitative map for the abundance and interactions of 16 factors related to PCH in living cells and found that stably bound complexes of the histone methyltransferase SUV39H1/2 demarcate the PCH state. From the experimental data, we developed a predictive mathematical model that explains how chromatin‐bound SUV39H1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H3 lysine 9 trimethylation levels via chromatin dynamics. This “nucleation and looping” mechanism is particularly robust toward transient perturbations and stably maintains the PCH state. These features make it an attractive model for establishing functional epigenetic domains throughout the genome based on the localized immobilization of chromatin‐modifying enzymes. |
| format | Article |
| id | doaj-art-7ec5480278904b7987d9ffaba1bb9dda |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2014-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-7ec5480278904b7987d9ffaba1bb9dda2025-08-20T04:03:12ZengSpringer NatureMolecular Systems Biology1744-42922014-08-0110812210.15252/msb.20145377Specificity, propagation, and memory of pericentric heterochromatinKatharina Müller‐Ott0Fabian Erdel1Anna Matveeva2Jan‐Philipp Mallm3Anne Rademacher4Matthias Hahn5Caroline Bauer6Qin Zhang7Sabine Kaltofen8Gunnar Schotta9Thomas Höfer10Karsten Rippe11Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionDivision Theoretical Systems Biology, Deutsches Krebsforschungszentrum (DKFZ) and BioQuantDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionMunich Center for Integrated Protein Science and Adolf Butenandt Institute, Ludwig Maximilians UniversityDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionDivision Theoretical Systems Biology, Deutsches Krebsforschungszentrum (DKFZ) and BioQuantDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionMunich Center for Integrated Protein Science and Adolf Butenandt Institute, Ludwig Maximilians UniversityDivision Theoretical Systems Biology, Deutsches Krebsforschungszentrum (DKFZ) and BioQuantDeutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & FunctionAbstract The cell establishes heritable patterns of active and silenced chromatin via interacting factors that set, remove, and read epigenetic marks. To understand how the underlying networks operate, we have dissected transcriptional silencing in pericentric heterochromatin (PCH) of mouse fibroblasts. We assembled a quantitative map for the abundance and interactions of 16 factors related to PCH in living cells and found that stably bound complexes of the histone methyltransferase SUV39H1/2 demarcate the PCH state. From the experimental data, we developed a predictive mathematical model that explains how chromatin‐bound SUV39H1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H3 lysine 9 trimethylation levels via chromatin dynamics. This “nucleation and looping” mechanism is particularly robust toward transient perturbations and stably maintains the PCH state. These features make it an attractive model for establishing functional epigenetic domains throughout the genome based on the localized immobilization of chromatin‐modifying enzymes.https://doi.org/10.15252/msb.20145377FRAP/FCSheterochromatin protein 1histone methylationpericentric heterochromatinprotein network |
| spellingShingle | Katharina Müller‐Ott Fabian Erdel Anna Matveeva Jan‐Philipp Mallm Anne Rademacher Matthias Hahn Caroline Bauer Qin Zhang Sabine Kaltofen Gunnar Schotta Thomas Höfer Karsten Rippe Specificity, propagation, and memory of pericentric heterochromatin Molecular Systems Biology FRAP/FCS heterochromatin protein 1 histone methylation pericentric heterochromatin protein network |
| title | Specificity, propagation, and memory of pericentric heterochromatin |
| title_full | Specificity, propagation, and memory of pericentric heterochromatin |
| title_fullStr | Specificity, propagation, and memory of pericentric heterochromatin |
| title_full_unstemmed | Specificity, propagation, and memory of pericentric heterochromatin |
| title_short | Specificity, propagation, and memory of pericentric heterochromatin |
| title_sort | specificity propagation and memory of pericentric heterochromatin |
| topic | FRAP/FCS heterochromatin protein 1 histone methylation pericentric heterochromatin protein network |
| url | https://doi.org/10.15252/msb.20145377 |
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