title: Stabilization of epigenetic states of CpG islands by local cooperation.
abstract: DNA methylation of CpG sites is an important epigenetic mark in mammals. Active promoters are often associated with unmethylated CpG sites, whereas methylated CpG sites correlate with silenced promoters. Methylation of CpG sites must be generally described as a dynamical process that is mediated by methylation enzymes, such as DNMT1 and DNMT3a/b. However, there are several models of how CpG sites can be protected from methylation and thereby remain unmethylated. In this paper we examine the combination of both: the positive feedbacks of DNA methylation and a short range counterpart which in turn protects-and thereby maintains-the unmethylated state. The emergent dynamics is provided by collaborative, re-enforcing feedbacks in favor of methylated CpG islands and cooperative protection of one CpG site by another in favor of unmethylated CpG sites. Our results suggest that this synthesis of mechanisms provides equally robust maintenance of both the unmethylated and methylated states of CpG islands.
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. sneppen@nbi.ku.dk.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sormani
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. sneppen@nbi.ku.dk.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Haerter
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. sneppen@nbi.ku.dk.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lövkvist
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. sneppen@nbi.ku.dk.
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D006657:Histones / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes