Abstract
Epigenetics is the study of the heritable changes in gene expression that occur without a change in the DNA sequence itself. These heritable epigenetic changes include chromatin folding and attachment to the nuclear matrix, packaging of DNA around nucleosomes, histone modifications, and DNA methylation. The epigenome is particularly susceptible to dysregulation during gestation, neonatal development, puberty, and old age. Nevertheless, it is most vulnerable to environmental factors during embryogenesis because the DNA synthetic rate is high, and the elaborate DNA methylation patterning and chromatin structure required for normal tissue development is established during early development. Metastable epialleles are alleles that are variably expressed in genetically identical individuals due to epigenetic modifications established during early development and are thought to be particularly vulnerable to environmental influences. The viable yellow agouti (Avy) allele, whose expression is correlated to DNA methylation, is a murine metastable epiallele, which has been used as an epigenetic biosensor for environmental factors affecting the fetal epigenome. In this review, we introduce epigenetic gene regulation, describe important epigenetic phenomenon in mammals, summarize literature linking the early environment to developmental plasticity of the fetal epigenome, and promote the necessity to identify epigenetically labile genes in the mouse and human genomes.
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Abbreviations
- A :
-
agouti
- A vy :
-
viable yellow agouti
- Axin fu :
-
axin fused
- CpG:
-
cytosine-guanine dinucleotide
- IAP:
-
intracisternal A particle
- LOI:
-
loss of imprinting
- RISC:
-
RNA-induced silencing complex
- RITS:
-
RNA-induced initiation of transcriptional silencing
- SAM:
-
S-adenosylmethionine
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This work was supported by DOE grant DE-FG02-05ER64101 and National Institutes of Health grants ES13053, ES08823, ES015165, and T32-ES07031.
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Dolinoy, D., Das, R., Weidman, J. et al. Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases. Pediatr Res 61, 30–37 (2007). https://doi.org/10.1203/pdr.0b013e31804575f7
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DOI: https://doi.org/10.1203/pdr.0b013e31804575f7
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