DNA methylation in health and disease

  title={DNA methylation in health and disease},
  author={Keith D. Robertson and Alan P. Wolffe},
  journal={Nature Reviews Genetics},
DNA methylation has recently moved to centre stage in the aetiology of human neurodevelopmental syndromes such as the fragile X, ICF and Rett syndromes. These diseases result from the misregulation of genes that occurs with the loss of appropriate epigenetic controls during neuronal development. Recent advances have connected DNA methylation to chromatin-remodelling enzymes, and understanding this link will be central to the design of new therapeutic tools. 
DNA methylation and human disease
A large number of human diseases have been found to be associated with aberrant DNA methylation and the study of these diseases has provided new and fundamental insights into the roles that DNAmethylation and other epigenetic modifications have in development and normal cellular homeostasis.
Epigenetics: Influence on Behavioral Disorders
The epigenetic modifications of the genome are critically important for normal functioning of a cell and may represent a fundamental mechanism of human diseases.
DNA methylation 40 years later: Its role in human health and disease
The impact of the studies on DNA methylation, the “primadonna” in the epigenetic scenario, on the understanding of basic phenomena, such as X inactivation and genomic imprinting is reviewed.
DNA methylation, genomic silencing, and links to nutrition and cancer.
The purpose of this review is to examine the relationship between dietary methyl insufficiency and DNA methylation, and to evaluate the associations betweenDNA methylation and cancer.
DNA methylation signature analysis: how easy is it to perform?
DNA methylation signature analysis by methylation-specific polymerase chain reaction has been a breakthrough method in speed and sensitivity for gene methylation studies, but several factors still limit its application as a routine diagnostic and prognostic test.
Methylated Cytosine and the Brain A New Base for Neuroscience
DNA methylation in mammalian development and disease.
DNA methylation has been implicated in a wide range of biological functions, including an essential developmental role in the reprogramming of germ cells and early embryos, the repression of endogenous retrotransposons, and a generalized role in gene expression.
Mammalian DNA methyltransferases.
A great progress has been made in understanding of the enzymatic machinery involved in establishing and maintaining methylation patterns, which allowed for the development of new diagnostic tools and epigenetic treatment therapies and the new approaches hold a great potential.
DNA methylation: The nuts and bolts of repression
The mechanisms which lead to the long‐term silencing of genes are discussed and the progression that has been made in determining the targeted mechanisms for de novo DNA methylation is surveyed.
econfiguration of DNA methylation in aging
Surprisingly, specific DNA regions show directional epigenetic changes in aged Erschienen, characterized by gradual extensive demethylation of genome and hypermethylation of a number of promoterassociated CpG islands.


Cancer-epigenetics comes of age
Current mechanistic understanding of the role of DNA methylation in malignant transformation is reviewed, and it is suggested Knudson's two–hit hypothesis should be expanded to include epigenetic mechanisms of gene inactivation.
The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome.
The first example of naturally occurring mutations in a mammalian DNA methyltransferase gene is described, occurring in patients with a rare autosomal recessive disorder, termed the ICF syndrome, for immunodeficiency, centromeric instability, and facial anomalies.
DNA methylation and imprinting: why bother?
Epigenetics and its role in disease.
The articles collected here consider in some detail the consequences of epigenetic effects for human disease phenotypes, and whether lesions in human disease genes can be partly or entirely epigenetic.
DNA hypomethylation leads to elevated mutation rates
It is reported that murine embryonic stem cells nullizygous for the major DNA methyl transferase (Dnmt1) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and an integrated viral thymidine kinase (tk) transgene, implying an important role for mammalian DNA methylation in maintaining genome stability.
Maintenance of genomic methylation requires a SWI2/SNF2-like protein
It is reported that DDM1 encodes a SWI2/SNF2-like protein, implicating chromatin remodelling as an important process for maintenance of DNA methylation and genome integrity.
CpG methylation is maintained in human cancer cells lacking DNMT1
It is shown that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation, indicating thatDNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DN MT1 can maintain the methylation of most of the genome.
Cytosine methylation and the ecology of intragenomic parasites.
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
The results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.
An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome.
The methylation deficiency affects classical satellite families built from distinct unit sequences but located in the same chromosomal region, which may have important implications for the mechanism of chromosomal rearrangements.