Cited by 7,124Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

DNA methylation patterns and epigenetic memory

Open access
Bird, Adrian·2002·Genes & Development

Abstract

The character of a cell is defined by its constituent proteins, which are the result of specific patterns of gene expression. Crucial determinants of gene expression patterns are DNA-binding transcription factors that choose genes for transcriptional activation or repression by recognizing the sequence of DNA bases in their promoter regions. Interaction of these factors with their cognate sequences triggers a chain of events, often involving changes in the structure of chromatin, that leads to the assembly of an active transcription complex (e.g., Cosma et al. 1999). But the types of transcription factors present in a cell are not alone sufficient to define its spectrum of gene activity, as the transcriptional potential of a genome can become restricted in a stable manner during development. The constraints imposed by developmental history probably account for the very low efficiency of cloning animals from the nuclei of differentiated cells (Rideout et al. 2001; Wakayama and Yanagimachi 2001). A “transcription factors only” model would predict that the gene expression pattern of a differentiated nucleus would be completely reversible upon exposure to a new spectrum of factors. Although many aspects of expression can be reprogrammed in this way (Gurdon 1999), some marks of differentiation are evidently so stable that immersion in an alien cytoplasm cannot erase the memory. The genomic sequence of a differentiated cell is thought to be identical in most cases to that of the zygote from which it is descended (mammalian B and T cells being an obvious exception). This means that the marks of developmental history are unlikely to be caused by widespread somatic mutation. Processes less irrevocable than mutation fall under the umbrella term “epigenetic” mechanisms. A current definition of epigenetics is: “The study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence” (Russo et al. 1996). There are two epigenetic systems that affect animal development and fulfill the criterion of heritability: DNA methylation and the Polycomb-trithorax group (Pc-G/trx) protein complexes. (Histone modification has some attributes of an epigenetic process, but the issue of heritability has yet to be resolved.) This review concerns DNA methylation, focusing on the generation, inheritance, and biological significance of genomic methylation patterns in the development of mammals. Data will be discussed favoring the notion that DNA methylation may only affect genes that are already silenced by other mechanisms in the embryo. Embryonic transcription, on the other hand, may cause the exclusion of the DNA methylation machinery. The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development. Indeed, the possibility will be discussed that DNA methylation and Pc-G/trx may represent alternative systems of epigenetic memory that have been interchanged over evolutionary time. Animal DNA methylation has been the subject of several recent reviews (Bird and Wolffe 1999; Bestor 2000; Hsieh 2000; Costello and Plass 2001; Jones and Takai 2001). For recent reviews of plant and fungal DNA methylation, see Finnegan et al. (2000), Martienssen and Colot (2001), and Matzke et al. (2001).

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Crossref · 10.1101/gad.947102

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  • DNA methylation in promoter regions blocks transcription factors from binding and reduces or silences gene expression.

    “When methylation occurs within promoter regions, transcription factors are blocked from binding and gene expression is reduced or silenced”

    From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [9]

    The “Mechanisms of DNA methylation-mediated transcriptional repression” section says that methylation prevents some proteins from binding DNA and describes this as one mode of repression. It also describes a second mode and an example in which blocked CTCF binding allows Igf2 expression. Thus, the source does not support the claim that promoter methylation generally blocks transcription-factor binding and thereby reduces or silences expression. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • DNA is methylated at the C5 position of cytosine.

    “DNA itself is also subject to methylation on the C5 atom of cytosine (Bird, 2002).”

    From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Bird, 2002

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Research works printed but not linked: 1

  1. Wolffe, A.P., Jones, P.L., and Wade, P.A. 1999. DNA demethyl- ation. Proc. Natl. Acad. Sci. 96: 5894-5896.

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Authors
Bird, A.
Affiliations
Wellcome Centre for Cell Biology (GB)
Corresponding author
Bird, Adrian
Venue
Genes & Development
Published
2002-01-01
Volume
16
Issue
1
Pages
6-21
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2121417064
Cited by
7,124
References
207
Citations by year
2026: 178 · 2025: 199 · 2024: 247 · 2023: 222 · 2022: 284 · 2021: 327 · 2020: 318 · 2019: 328 · 2018: 327 · 2017: 426 · 2016: 408 · 2015: 416 · 2014: 415 · 2013: 409 · 2012: 382
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
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
epigenetic memory, genomic imprinting, Polycomb group proteins, Trithorax group proteins, transcriptional repression, epigenetic reprogramming, mammalian development, gene silencing, histone modifications, somatic cell nuclear transfer, epigenetic inheritance
MeSH terms
Animals, Embryonic and Fetal Development, Humans, Transcription, Genetic, Gene Expression Regulation, Developmental, DNA Methylation, Gene Silencing

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