Molecular Systems Biology | |
Specificity, propagation, and memory of pericentric heterochromatin | |
Katharina Müller-Ott2  Fabian Erdel2  Anna Matveeva1  Jan-Philipp Mallm2  Anne Rademacher2  Matthias Hahn3  Caroline Bauer2  Qin Zhang1  Sabine Kaltofen2  Gunnar Schotta3  Thomas Höfer1  | |
[1] Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Division Theoretical Systems Biology, Heidelberg, Germany;Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany;Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany | |
关键词: FRAP/FCS; heterochromatin protein 1; histone methylation; pericentric heterochromatin; protein network; | |
DOI : 10.15252/msb.20145377 | |
来源: Wiley | |
【 摘 要 】
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. A comprehensive analysis of the epigenetic network that silences pericentric heterochromatin (PCH) transcription in mouse fibroblasts is presented. The resulting quantitative model explains the spatial extension, stability and propagation of histone modification domains.Abstract
Synopsis
【 授权许可】
CC BY
© 2014 The Authors. Published under the terms of the CC BY 4.0 license
Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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