Impact of Epigenetic Dietary Compounds on Transgenerational Prevention of Human Diseases

Abstract

The etiology of most human diseases involves complicated interactions of multiple environmental factors with individual genetic background which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Early embryogenesis includes a series of programming processes involving extremely accurate time-controlled gene activation/silencing expressions, and epigenetic control is believed to play a key role in regulating early embryonic development. Certain dietary components with properties in influencing epigenetic processes are believed to have preventive effects on many human diseases such as cancer. Evidence shows that in utero exposure to certain epigenetic diets may lead to reprogramming of primary epigenetic profiles such as DNA methylation and histone modifications on the key coding genes of the fetal genome, leading to different susceptibility to diseases later in life. In this review, we assess the current advances in dietary epigenetic intervention on transgenerational human disease control. Enhanced understanding of the important role of early life epigenetics control may lead to cost-effective translational chemopreventive potential by appropriate administration of prenatal and/or postnatal dietary supplements leading to early disease prevention.

Fig. 1

Maternal epigenetic diets regulate DNA methylation and histone modifications during embryogenesis. a DNA methylation reprogramming during early embryonic development. After fertilization, genomic DNA undergoes a passive demethylation process and parental DNA methylation markers are erased except imprinting genes. The methylation level of a blastocyst reaches the lowest point. After implantation, a genome-wide remethylation phase occurs through an active de novo methylation regulated by DNMT3a/3b. Cellular and organ-specific methylation patterns are maintained by DNMT1 throughout life in the somatic cells. b Histone modification during embryogenesis. Transcriptional regulators of cell differentiation lineages are mainly regulated by histone methylation and acetylation. Histone methylation is mediated by HMT, and either gene activation or repression by histone methylation is dependent upon the particular lysine residue that is modified. Histone acetylation is mediated by HAT and deacetylation is catalyzed by the HDAC family. Histone acetylation causes an open chromatin structure leading to active transcription, whereas histone deacetylation is always associated with transcriptional repression. DNMT DNA methyltransferases, HAT histone acetyltransferases, HDAC histone deacetylase, HMT histone methyltransferase

Fig. 2

The timing of epigenetic diet exposure throughout life. The top row indicates the importance of different epigenetic dietary exposure that may affect the epigenome and have later-life consequences. For example, early consumption of genistein during childhood and adolescence in women reduces later mammary cancer risk, whereas maternal/adult exposure to GE may be considered to be a risk factor to induce breast cancer. The middle row represents different lifetime periods including prenatal, gestation, lactation, puberty, and maturation periods. The bottom row indicates important epigenetic events in different stages of life. GE genistein; check mark indicates potential protective effects of GE consumption on prevention of breast cancer; cross indicates the potential risk factors of GE consumption to the development of breast cancer; question mark indicates an unknown effect of GE consumption on breast cancer development