Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation
DNA methylation is a heritable epigenetic mark that plays a key role in regulating gene expression. Mathematical modeling has been extensively applied to unravel the regulatory mechanisms of this process. In this study, we aimed to investigate DNA methylation by performing a high-depth analysis of p...
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doaj-1caa4ca709e74034acdd569764f7ab372020-11-25T03:18:51ZengMDPI AGBiomolecules2218-273X2020-09-01101271127110.3390/biom10091271Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and DemethylationGiulia De Riso0Damiano Francesco Giuseppe Fiorillo1Annalisa Fierro2Mariella Cuomo3Lorenzo Chiariotti4Gennaro Miele5Sergio Cocozza6Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Via S. Pansini 5, 80131 Naples, ItalyDipartimento di Fisica “E. Pancini”, Università degli Studi di Napoli “Federico II”, 80126, Naples, ItalyCNR-SPIN, c/o Complesso di Monte S. Angelo, via Cinthia, 80126 Naples, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Via S. Pansini 5, 80131 Naples, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Via S. Pansini 5, 80131 Naples, ItalyDipartimento di Fisica “E. Pancini”, Università degli Studi di Napoli “Federico II”, 80126, Naples, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Via S. Pansini 5, 80131 Naples, ItalyDNA methylation is a heritable epigenetic mark that plays a key role in regulating gene expression. Mathematical modeling has been extensively applied to unravel the regulatory mechanisms of this process. In this study, we aimed to investigate DNA methylation by performing a high-depth analysis of particular loci, and by subsequent modeling of the experimental results. In particular, we performed an in-deep DNA methylation profiling of two genomic loci surrounding the transcription start site of the D-Aspartate Oxidase and the D-Serine Oxidase genes in different samples (n = 51). We found evidence of cell-to-cell differences in DNA methylation status. However, these cell differences were maintained between different individuals, which indeed showed very similar DNA methylation profiles. Therefore, we hypothesized that the observed pattern of DNA methylation was the result of a dynamic balance between DNA methylation and demethylation, and that this balance was identical between individuals. We hence developed a simple mathematical model to test this hypothesis. Our model reliably captured the characteristics of the experimental data, suggesting that DNA methylation and demethylation work together in determining the methylation state of a locus. Furthermore, our model suggested that the methylation status of neighboring cytosines plays an important role in this balance.https://www.mdpi.com/2218-273X/10/9/1271DNA methylationDNA demethylationmathematical modelingstatistical equilibriumcell-to-cell heterogeneitymethylation profiles |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giulia De Riso Damiano Francesco Giuseppe Fiorillo Annalisa Fierro Mariella Cuomo Lorenzo Chiariotti Gennaro Miele Sergio Cocozza |
spellingShingle |
Giulia De Riso Damiano Francesco Giuseppe Fiorillo Annalisa Fierro Mariella Cuomo Lorenzo Chiariotti Gennaro Miele Sergio Cocozza Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation Biomolecules DNA methylation DNA demethylation mathematical modeling statistical equilibrium cell-to-cell heterogeneity methylation profiles |
author_facet |
Giulia De Riso Damiano Francesco Giuseppe Fiorillo Annalisa Fierro Mariella Cuomo Lorenzo Chiariotti Gennaro Miele Sergio Cocozza |
author_sort |
Giulia De Riso |
title |
Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation |
title_short |
Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation |
title_full |
Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation |
title_fullStr |
Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation |
title_full_unstemmed |
Modeling DNA Methylation Profiles through a Dynamic Equilibrium between Methylation and Demethylation |
title_sort |
modeling dna methylation profiles through a dynamic equilibrium between methylation and demethylation |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2020-09-01 |
description |
DNA methylation is a heritable epigenetic mark that plays a key role in regulating gene expression. Mathematical modeling has been extensively applied to unravel the regulatory mechanisms of this process. In this study, we aimed to investigate DNA methylation by performing a high-depth analysis of particular loci, and by subsequent modeling of the experimental results. In particular, we performed an in-deep DNA methylation profiling of two genomic loci surrounding the transcription start site of the D-Aspartate Oxidase and the D-Serine Oxidase genes in different samples (n = 51). We found evidence of cell-to-cell differences in DNA methylation status. However, these cell differences were maintained between different individuals, which indeed showed very similar DNA methylation profiles. Therefore, we hypothesized that the observed pattern of DNA methylation was the result of a dynamic balance between DNA methylation and demethylation, and that this balance was identical between individuals. We hence developed a simple mathematical model to test this hypothesis. Our model reliably captured the characteristics of the experimental data, suggesting that DNA methylation and demethylation work together in determining the methylation state of a locus. Furthermore, our model suggested that the methylation status of neighboring cytosines plays an important role in this balance. |
topic |
DNA methylation DNA demethylation mathematical modeling statistical equilibrium cell-to-cell heterogeneity methylation profiles |
url |
https://www.mdpi.com/2218-273X/10/9/1271 |
work_keys_str_mv |
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