Cited by 471Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

DNA methylation and chromatin – unraveling the tangled web

Robertson, Keith D·2002·Oncogene

Abstract

Methylation of cytosines within the CpG dinucleotide by DNA methyltransferases is involved in regulating transcription and chromatin structure, controlling the spread of parasitic elements, maintaining genome stability in the face of vast amounts of repetitive DNA, and X chromosome inactivation. Cellular DNA methylation is highly compartmentalized over the mammalian genome and this compartmentalization is essential for embryonic development. When the complicated mechanisms that control which DNA sequences become methylated go awry, a number of inherited genetic diseases and cancer may result. Much new information has recently come to light regarding how cellular DNA methylation patterns may be established during development and maintained in somatic cells. Emerging evidence indicates that various chromatin states such as histone modifications (acetylation and methylation) and nucleosome positioning (modulated by ATP-dependent chromatin remodeling machines) determine DNA methylation patterning. Additionally, various regulatory factors interacting with the DNA methyltransferases may direct them to specific DNA sequences, regulate their enzymatic activity, and allow their use as transcriptional repressors. Continued studies of the connections between DNA methylation and chromatin structure and the DNA methyltransferase-associated proteins, will likely reveal that many, if not all, epigenetic modifications of the genome are directly connected. Such studies should also yield new insights into treating diseases involving aberrant DNA methylation.

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Crossref · 10.1038/sj.onc.1205609

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  • Unmethylated CpG islands in a gene's promoter region are typically associated with higher expression of that gene.

    “in contrast, if the CpG islands in the promoter region remain unmethylated, the gene is typically more highly expressed.20,21”

    From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [21]

  • Methylation of CpG islands in a gene's promoter region may downregulate or transcriptionally silence that gene's expression.

    “If the CpG islands of the promoter region for a particular gene are methylated, the expression of that gene may be downregulated or transcriptionally silenced;”

    From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [21]

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Authors
Robertson, K. D.
Affiliations
National Institutes of Health (US)
Corresponding author
Robertson, Keith D
Venue
Oncogene
Published
2002-08-05
Volume
21
Issue
35
Pages
5361-5379
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2002129512
Cited by
471
References
133
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 16 · 2022: 17 · 2021: 20 · 2020: 22 · 2019: 14 · 2018: 7 · 2017: 18 · 2016: 18 · 2015: 20 · 2014: 25 · 2013: 23 · 2012: 22
FWCI
2.26
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA84535-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
DNA methylation, chromatin structure, DNA methyltransferases, CpG, histone modifications, nucleosome positioning, chromatin remodeling, X chromosome inactivation, genome stability, repetitive DNA, embryonic development, epigenetic regulation, transcriptional repression, cancer epigenetics, genetic disorders
MeSH terms
Acetylation, Adenosine Triphosphatases, Animals, Chromatin, Disease Models, Animal, DNA Helicases, DNA-Binding Proteins, Gene Expression Regulation, Histone Deacetylases, Histones, Humans, Methyltransferases, Nuclear Proteins, Syndrome, Transcription Factors, Transcription, Genetic, DNA Methylation, Gene Silencing

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