title: The Influence of Hydroxylation on Maintaining CpG Methylation Patterns: A Hidden Markov Model Approach.
abstract: DNA methylation and demethylation are opposing processes that when in balance create stable patterns of epigenetic memory. The control of DNA methylation pattern formation by replication dependent and independent demethylation processes has been suggested to be influenced by Tet mediated oxidation of 5mC. Several alternative mechanisms have been proposed suggesting that 5hmC influences either replication dependent maintenance of DNA methylation or replication independent processes of active demethylation. Using high resolution hairpin oxidative bisulfite sequencing data, we precisely determine the amount of 5mC and 5hmC and model the contribution of 5hmC to processes of demethylation in mouse ESCs. We develop an extended hidden Markov model capable of accurately describing the regional contribution of 5hmC to demethylation dynamics. Our analysis shows that 5hmC has a strong impact on replication dependent demethylation, mainly by impairing methylation maintenance.
authors.affiliation: Department of Biological Sciences, UdS, Saarbrücken, Saarland, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Giehr
authors.affiliation: Computer Science Department, UdS, Saarbrücken, Saarland, Germany.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Kyriakopoulos
authors.affiliation: Barts Cancer Institute, Queen Mary University, London, United Kingdom.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ficz
authors.affiliation: Computer Science Department, UdS, Saarbrücken, Saarland, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Wolf
authors.affiliation: Department of Biological Sciences, UdS, Saarbrücken, Saarland, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D004261:DNA Replication; D053595:Embryonic Stem Cells / Q000378:metabolism; D006900:Hydroxylation; D008390:Markov Chains; D051379:Mice; D008954:Models, Biological; D013269:Stochastic Processes; D013447:Sulfites / Q000378:metabolism
chemical_list: D013447:Sulfites; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; C042345:hydrogen sulfite