Editors' ChoiceEpigenetics

Childhood memory

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Science Translational Medicine  29 Apr 2015:
Vol. 7, Issue 285, pp. 285ec71
DOI: 10.1126/scitranslmed.aab3137

Early-life events echo in the memory—epigenetic memory, that is: inheritable modifications that do not change the underlying genomic sequence. Cell typespecific DNA methylation often occurs during fetal development, and cellular differentiation and maturation. Some of these acquired DNA methylation signatures are maintained during mitosis (epigenetic memory) whereas others vary across one’s lifespan and are influenced by diseases, lifestyle, environmental factors, and genetic variation. Scientists have studied age-related changes in DNA methylation but most investigations were performed in adults. The cataloging of age-associated changes in DNA methylation during early childhood in healthy individuals would establish a foundation for epigenetic studies in children. Now, Acevedo and colleagues describe a well-designed prospective study that begins to elucidate the dynamics of DNA methylation in blood leukocytes during infancy to the early childhood period.

After carefully filtering out known genotypic and cell lineage-specific signatures, the authors pinpointed 794 age-associated DNA methylation changes in leukocytes taken from 10 female subjects at 7 time points between 3 months and 5 years of age. Age-specific modifications (methylation or demethylation) of genomic CpG sites showed differential distributions within gene structures. Age-related methylation of CpG sites was significantly overrepresented in the coding regions of developmental genes as well as those that were specifically expressed in neurons. In contrast, age-related demethylation of CpGs sites was localized in gene promoters and DNaseI-hypersensitive sites and enriched in genes tied to immune function and those that encode components of the polycomb-group protein complex, a regulator of chromatin structure. These results suggested that DNA methylation changes related to age might not result only from a stochastic drift but rather correspond to a program with potential functional relevance in leukocyte biology during early childhood. This study not only ignites our understanding of leukocyte maturation during the first years of life but also provides a comparison catalog with which to correct for age effects when performing DNA methylation studies in children.

The most glaring limitation of the new work is that factors such as genetic variation, gender, and environmental exposures—including the in utero environment—might also affect the dynamics of DNA methylation, and they were not controlled for in this study. The authors are conducting an ongoing larger prospective study that includes subjects of both genders exposed to different lifestyles.

N. Acevedo et al., Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes. Clin. Epigenet. 7, 34 (2015). [Full Text]

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