On the Biological Significance of DNA Methylation

Abstract

This chapter presents a personal account of the work on DNA methylation in viral and mammalian systems performed in the author's laboratory in the course of the past thirty years. The text does not attempt to give a complete and meticulous account of the many relevant and excellent reports published by many other laboratories, so it is not a review of the field in a conventional sense. The choice of viral model systems in molecular biology is well founded. Over many decades, viruses have proven their invaluable and pioneering role as tools in molecular genetics. When our interest turned to the demonstration of genome-wide patterns of DNA methylation, we focused mainly on the human genome. The following topics in DNA methylation will be treated in detail: (i) the de novo methylation of integrated foreign genomes; (ii) the long-term gene silencing effect of sequence-specific promoter methylation and its reversal; (iii) the properties and specificity of patterns of DNA methylation in the human genome and their possible relations to pathogenesis; (iv) the long-range global effects on cellular DNA methylation and transcriptional profiles as a consequence of foreign DNA insertion into an established genome; (v) the patterns of DNA methylation can be considered part of a cellular defense mechanism against foreign or repetitive DNA; what role has food-ingested DNA played in the elaboration of this mechanism?

Molecular cloning and characterization of the DNA adenine methyltransferase gene in Feldmannia sp. virus

“…Although DNA modification such as methylation is rarely observed in plant or animal virus genomes [12], modified bases are more common in the genomes of bacteriophages [13]. In fact, certain bacteriophages encode DNA-adenine MTases [14,15].…”

DNA-remethylation around a STAT5-binding enhancer in the αS1-casein promoter is associated with abrupt shutdown of αS1-casein synthesis during acute mastitis

“…Aberrant methylation plays a role in the development of chronic diseases and cancer (McCabe & Caudill 2005, Ushijima & Okochi--Takada 2005. Examples for de novo CpG methylation are mostly associated with the silencing of foreign DNA, introduced either by viruses or as artificial transgenes (Doerfler 2005). However, there are no examples demonstrating occurrence and regulatory significance of de novo methylation during an acute, physiological reprogramming of the cellular metabolism.…”

DNA Methylation

“…Modern concepts are more explicit when describing the link between the long-term inactivation through CpG island methylation and the short-term methylation in bulk CpG stretches needed for tissue specific gene expression control (Doerfler, 2005(Doerfler, , 2006. Recently, however, CpG islands' methylation has been admitted as having functional relevance for permanent inactivation of X-chromosome and for specific imprinting in chromosomal regions of autosomal genes, in order to mark the parental-specific gene expression pattern (Li and Bird, 2007;Cedar and Bergman, 2009).…”