title: 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 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.
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Müller-Ott
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Erdel
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Division Theoretical Systems Biology, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Matveeva
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Mallm
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Rademacher
authors.affiliation: Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Division Theoretical Systems Biology, Heidelberg, Germany.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kaltofen
authors.affiliation: Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Division Theoretical Systems Biology, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Research Group Genome Organization & Function, Heidelberg, Germany karsten.rippe@dkfz.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020868:Gene Silencing; D005819:Genetic Markers; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D054730:Protein Interaction Domains and Motifs; D012091:Repetitive Sequences, Nucleic Acid; D012680:Sensitivity and Specificity
chemical_list: C453799:Cbx3 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D005819:Genetic Markers; D006570:Heterochromatin; D006657:Histones; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D011495:Histone-Lysine N-Methyltransferase
keywords: FRAP/FCS; heterochromatin protein 1; histone methylation; pericentric heterochromatin; protein network