title: Non-canonical functions of the DNA methylome in gene regulation.
abstract: Methylation of the cytosine base in DNA, DNA methylation, is an essential epigenetic mark in mammals that contributes to the regulation of transcription. Several advances have been made in this area in recent years, leading to a leap forward in our understanding of how this pathway contributes to gene regulation during embryonic development, and the functional consequences of its perturbation in human disease. Critical to these advances is a comprehension of the genomic distribution of modified cytosine bases in unprecedented detail, drawing attention to genomic regions beyond gene promoters. In addition, we have a more complete understanding of the multifactorial manner by which DNA methylation influences gene regulation at the molecular level, and which genes rely directly on the DNA methylome for their normal transcriptional regulation. It is becoming apparent that a major role of DNA modification is to act as a relatively stable, and mitotically heritable, template that contributes to the establishment and maintenance of chromatin states. In this regard, interplay is emerging between DNA methylation and the PcG (Polycomb group) proteins, which act as evolutionarily conserved mediators of cell identity. In the present paper we review these aspects of DNA methylation, and discuss how a multifunctional view of DNA modification as an integral part of chromatin organization is influencing our understanding of this epigenetic mark's contribution to transcriptional regulation.
authors.affiliation: MRC Human Genetics Unit, MRC IGMM (Institute of Genetics and Molecular Medicine), University of Edinburgh, Western General Hospital, Crewe Rd, Edinburgh EH4 1SX, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Reddington
authors.forename: Sari
authors.initials: S
authors.lastname: Pennings
authors.forename: Richard R
authors.initials: RR
authors.lastname: Meehan
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D006801:Humans; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D063146:Polycomb-Group Proteins