Specificity, propagation, and memory of pericentric heterochromatin

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Zeitschriftentitel:	Molecular Systems Biology
Personen und Körperschaften:	Müller‐Ott, Katharina, Erdel, Fabian, Matveeva, Anna, Mallm, Jan‐Philipp, Rademacher, Anne, Hahn, Matthias, Bauer, Caroline, Zhang, Qin, Kaltofen, Sabine, Schotta, Gunnar, Höfer, Thomas, Rippe, Karsten
In:	Molecular Systems Biology, 10, 2014, 8
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Springer Science and Business Media LLC
Schlagwörter:	Applied Mathematics Computational Theory and Mathematics General Agricultural and Biological Sciences General Immunology and Microbiology General Biochemistry, Genetics and Molecular Biology Information Systems

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Zusammenfassung:	<jats:title>Abstract</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">PCH</jats:styled-content>) of mouse fibroblasts. We assembled a quantitative map for the abundance and interactions of 16 factors related to <jats:styled-content style="fixed-case">PCH</jats:styled-content> in living cells and found that stably bound complexes of the histone methyltransferase <jats:styled-content style="fixed-case">SUV</jats:styled-content>39H1/2 demarcate the <jats:styled-content style="fixed-case">PCH</jats:styled-content> state. From the experimental data, we developed a predictive mathematical model that explains how chromatin‐bound <jats:styled-content style="fixed-case">SUV</jats:styled-content>39<jats:styled-content style="fixed-case">H</jats:styled-content>1/2 complexes act as nucleation sites and propagate a spatially confined <jats:styled-content style="fixed-case">PCH</jats:styled-content> domain with elevated histone <jats:styled-content style="fixed-case">H</jats:styled-content>3 lysine 9 trimethylation levels via chromatin dynamics. This “nucleation and looping” mechanism is particularly robust toward transient perturbations and stably maintains the <jats:styled-content style="fixed-case">PCH</jats:styled-content> 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.</jats:p>
ISSN:	1744-4292
DOI:	10.15252/msb.20145377