DNA methylation and the functional organization of the nuclear compartment

Abstract

Symmetrical methylation of cytosine residues at CpG dinucleotides of the DNA molecule is a central epigenetic and heritable hallmark of the genome. This epigenetic modification of DNA is directly associated with a closed molecular conformation of the chromatin fibre which is, in turn, intrinsically linked to an inactive transcriptional status. Thus, DNA methylation is a major determinant of the functional outcome of the nucleus. Equally important, DNA methylation is also involved in the large-scale maintenance of the nuclear architecture, which is required for proper nuclear function. Densely DNA methylated regions tend to occupy large and discrete regions of the genome and can act as referential structural blocks for building up the whole functional organization of the nucleus. In this context, interpreting the three-dimensional pattern of DNA methylation is crucial to our understanding of the dynamic biology of genomes. © 2009 Elsevier Ltd. All rights reserved.J.E. is a Ramon y Cajal Programme investigator, supported by the Spanish Ministry of Science and Innovation (SAF2008-00609). M.E. is an ICREA Research Professor supported by the Health (FIS PI08 1345) and Education and Science (I+D+I MCYT08-03 and Consolider MEC09-05) Departments of the Spanish Government, the Health Department of the Catalan Government and the European Union (FP7 CANCERDIP).Peer Reviewe