The diverse roles of DNA methylation in mammalian development and disease

  title={The diverse roles of DNA methylation in mammalian development and disease},
  author={Maxim V. C. Greenberg and Deborah Bourc’his},
  journal={Nature Reviews Molecular Cell Biology},
DNA methylation is of paramount importance for mammalian embryonic development. DNA methylation has numerous functions: it is implicated in the repression of transposons and genes, but is also associated with actively transcribed gene bodies and, in some cases, with gene activation per se. In recent years, sensitive technologies have been developed that allow the interrogation of DNA methylation patterns from a small number of cells. The use of these technologies has greatly improved our… 
The dynamic chromatin landscape and mechanisms of DNA methylation during mouse germ cell development
Deep sequencing, low-input methods and integrative analysis of chromatin marks in normal germ cells and in those deficient in chromatin-modifying enzymes uncovers a critical interplay between histone PTMs and de novo DNAme in the germline.
The roles of DNA, RNA and histone methylation in ageing and cancer
The cellular functions of chromatin methylation are discussed and a perspective on the emerging data from early-phase clinical trial therapies that target regulators of DNA and histone methylation is provided.
DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1
Recent advancements in understanding how DNA modifications contribute to tumor suppressor gene silencing or oncogenic-gene stimulation, as well as dysregulation of DNA methylation in cancer progression are outlined.
N6-Methyladenine in Eukaryotic DNA: Tissue Distribution, Early Embryo Development, and Neuronal Toxicity
It is demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and fetal development and exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats.
DNA methylation dynamics at transposable elements in mammals.
  • N. Jansz
  • Biology
    Essays in biochemistry
  • 2019
DNA methylation at transposable elements is discussed, describing its function and dynamic regulation throughout murine and human development.
A comprehensive epigenome atlas reveals DNA methylation regulating skeletal muscle development
The first single-base resolution DNA methylome and transcriptome maps of porcine skeletal muscle across 27 developmental stages are generated, highlighting the function and regulation of dynamic DNA methylation in skeletal muscle development.
Global reinforcement of DNA methylation through enhancement of RNA-directed DNA methylation ensures sexual reproduction in rice
It is demonstrated that a global increase of DNA methylation through enhancement of RdDM activity in reproductive organs ensures sexual reproduction of rice.
Locus-Specific DNA Methylation Editing in Melanoma Cell Lines Using a CRISPR-Based System
A comprehensive global workflow for the design and application of a dCas9-SunTag-based tool for editing the DNA methylation locus in human melanoma cells alongside protocols for downstream techniques used to evaluate subsequent methylation and gene expression changes in methylation-edited cells is described.
Roles and regulation of histone methylation in animal development
It has been revealed that methylation and demethylation of both activating and repressive marks are essential for establishing embryonic and extra-embryonic lineages, for ensuring gene dosage compensation via genomic imprinting and for establishing body patterning via HOX gene regulation.
Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing
It is concluded that in different cell types the consequence of DNA methylation on gene expression and cell fate can be completely different.


Targets and dynamics of promoter DNA methylation during early mouse development
This work optimized methylated DNA immunoprecipitation for low numbers of cells and profiled DNA methylation during early development of the mouse embryonic lineage in vivo, suggesting that escape of post-fertilizationDNA methylation reprogramming is prevalent in the mouse genome.
Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation
The data suggest that land plants and vertebrates are under strong selective pressure to repress TEs, because of their sexual mode of reproduction, and indicate that gene body methylation is an ancient property of eukaryotic genomes.
Charting a dynamic DNA methylation landscape of the human genome
Although in theory every CpG can change its methylation state, the results suggest that only a fraction does so as part of coordinated regulatory programs, which highlights the general inefficiency of whole-genome bisulphite sequencing.
The DNA methylation landscape of human early embryos
Insight is provided into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements, which indicate that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposability elements.
EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos.
DNA methylation is instrumental for EHMT2-mediated gene silencing in embryogenesis and is identified as a critical factor that facilitates repressive DNA methylation at specific genomic loci during mammalian development.
Human DNA methylomes at base resolution show widespread epigenomic differences
The first genome-wide, single-base-resolution maps of methylated cytosine methylation in a mammalian genome are presented, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA–protein interaction for several key regulatory factors.
Functions and mechanisms of epigenetic inheritance in animals
Insight from genome-wide studies suggest that a previously underappreciated fraction of mammalian genomes bypass epigenetic reprogramming during development, highlighting the importance of epigenetic inheritance in animals.
Dynamics and function of DNA methylation in plants
DNA methylation in plants mediates gene expression, transposon silencing, chromosome interactions and genome stability, and the regulation of DNA methylation is important for plant development and for plant responses to biotic and abiotic stresses.
A unique regulatory phase of DNA methylation in the early mammalian embryo
The data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.