Open AccessSpecificity, propagation, and memory of pericentric heterochromatin
Author(s) -
MüllerOtt Katharina,
Erdel Fabian,
Matveeva Anna,
Mallm JanPhilipp,
Rademacher Anne,
Hahn Matthias,
Bauer Caroline,
Zhang Qin,
Kaltofen Sabine,
Schotta Gunnar,
Höfer Thomas,
Rippe Karsten
Publication year - 2014
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20145377
Subject(s) - chromatin , heterochromatin , biology , epigenetics , histone , genetics , gene silencing , microbiology and biotechnology , histone methyltransferase , heterochromatin protein 1 , computational biology , gene
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 SUV 39H1/2 demarcate the PCH state. From the experimental data, we developed a predictive mathematical model that explains how chromatin‐bound SUV 39 H 1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H 3 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.