title: Modeling DNA methylation by analyzing the individual configurations of single molecules.
abstract: DNA methylation is often analyzed by reporting the average methylation degree of each cytosine. In this study, we used a single molecule methylation analysis in order to look at the methylation conformation of individual molecules. Using D-aspartate oxidase as a model gene, we performed an in-depth methylation analysis through the developmental stages of 3 different mouse tissues (brain, lung, and gut), where this gene undergoes opposite methylation destiny. This approach allowed us to track both methylation and demethylation processes at high resolution. The complexity of these dynamics was markedly simplified by introducing the concept of methylation classes (MCs), defined as the number of methylated cytosines per molecule, irrespective of their position. The MC concept smooths the stochasticity of the system, allowing a more deterministic description. In this framework, we also propose a mathematical model based on the Markov chain. This model aims to identify the transition probability of a molecule from one MC to another during methylation and demethylation processes. The results of our model suggest that: 1) both processes are ruled by a dominant class of phenomena, namely, the gain or loss of one methyl group at a time; and 2) the probability of a single CpG site becoming methylated or demethylated depends on the methylation status of the whole molecule at that time.
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore ," Consiglio Nazionale delle Ricerche (CNR) , Naples , Italy.|b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Affinito
authors.affiliation: c Istituto Nazionale di Fisica Nucleare , Sezione di Napoli , Naples , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scala
authors.affiliation: b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palumbo
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore ," Consiglio Nazionale delle Ricerche (CNR) , Naples , Italy.|b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Florio
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore ," Consiglio Nazionale delle Ricerche (CNR) , Naples , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Monticelli
authors.affiliation: c Istituto Nazionale di Fisica Nucleare , Sezione di Napoli , Naples , Italy.|d Dipartimento di Fisica , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Miele
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore ," Consiglio Nazionale delle Ricerche (CNR) , Naples , Italy.|b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Vittorio Enrico
authors.initials: VE
authors.lastname: Avvedimento
authors.affiliation: e CEINGE Biotecnologie Avanzate , Naples , Italy.|f Department of Environmental, Biological and Pharmaceutical Science and Technologies , Second University of Naples , Caserta , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Usiello
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore ," Consiglio Nazionale delle Ricerche (CNR) , Naples , Italy.|b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.|g Dipartimento di Farmacia , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Chiariotti
authors.affiliation: b Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli "Federico II ," Naples , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D013270:Stomach / Q000254:growth & development
chemical_list: D003596:Cytosine
keywords: DNA methylation analysis; DNA methylation model; epigenetics; methylation class; methylation/demethylation dynamics