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Open Access Highly Accessed Research article

A distinct group of CpG islands shows differential DNA methylation between replicas of the same cell line in vitro

Sergio Cocozza12, Giovanni Scala134, Gennaro Miele134, Imma Castaldo2* and Antonella Monticelli15

Author Affiliations

1 Gruppo Interdipartimentale di Bioinformatica e Biologia Computazionale, Università di Napoli “Federico II”, Naples, Italy

2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli “Federico II”, Naples, Italy

3 Dipartimento di Fisica, Università degli Studi di Napoli “Federico II”, Naples, Italy

4 Istituto Nazionale di Fisica Nucleare, Sezione di Napoli, Naples, Italy

5 Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS), CNR, Naples, Italy

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BMC Genomics 2013, 14:692  doi:10.1186/1471-2164-14-692

Published: 10 October 2013

Abstract

Background

CpG dinucleotide-rich genomic DNA regions, known as CpG islands (CGIs), can be methylated at their cytosine residues as an epigenetic mark that is stably inherited during cell mitosis. Differentially methylated regions (DMRs) are genomic regions showing different degrees of DNA methylation in multiple samples. In this study, we focused our attention on CGIs showing different DNA methylation between two culture replicas of the same cell line.

Results

We used methylation data of 35 cell lines from the Encyclopedia of DNA Elements (ENCODE) consortium to identify CpG islands that were differentially methylated between replicas of the same cell line and denoted them Inter Replicas Differentially Methylated CpG islands (IRDM-CGIs). We identified a group of IRDM-CGIs that was consistently shared by different cell lines, and denoted it common IRDM-CGIs. X chromosome CGIs were overrepresented among common IRDM-CGIs. Autosomal IRDM-CGIs were preferentially located in gene bodies and intergenic regions had a lower G + C content, a smaller mean length, and a reduced CpG percentage. Functional analysis of the genes associated with autosomal IRDM-CGIs showed that many of them are involved in DNA binding and development.

Conclusions

Our results show that several specific functional and structural features characterize common IRDM-CGIs. They may represent a specific subset of CGIs that are more prone to being differentially methylated for their intrinsic characteristics.

Keywords:
CpG Islands; Methylation; Differentially methylated regions; Epigenetics