Epigenetics and nutritional environmental signals

Abstract

All terrestrial life is influenced by multi-directional flows of information about its environment, enabling malleable phenotypic change through signals, chemical processes, or various forms of energy that facilitate acclimatization. Billions of biological co-inhabitants of the earth, including all plants and animals, collectively make up a genetic/epigenetic ecosystem by which adaptation/survival (inputs and outputs) are highly interdependent on one another. As an ecosystem, the solar system, rotation of the planets, changes in sunlight, and gravitational pull influence cyclic epigenetic transitions and chromatin remodeling that constitute biological circadian rhythms controlling senescence. In humans, adverse environmental conditions such as poverty, stress, alcohol, malnutrition, exposure to pollutants generated from industrialization, man-made chemicals, and use of synthetic drugs can lead to maladaptive epigenetic-related illnesses with disease-specific genes being atypically activated or silenced. Nutrition and dietary practices are one of the largest facets in epigenetic-related metabolism, where specific "epi-nutrients" can stabilize the genome, given established roles in DNA methylation, histone modification, and chromatin remodeling. Moreover, food-based "epi-bioactive" constituents may reverse maladaptive epigenetic patterns, not only prior to conception and during fetal/early postnatal development but also through adulthood. In summary, in contrast to a static genomic DNA structure, epigenetic changes are potentially reversible, raising the hope for therapeutic and/or dietary interventions that can reverse deleterious epigenetic programing as a means to prevent or treat major illnesses.

Fig. 1

Expression of genomic DNA is controlled by heritable epigenetic patterns that result in either transcriptional activated “euchromatin” (right panel) or silenced “heterochromatin” (left panel). [(A) The epigenome diverges from the genome at the level of DNA where CpG sites are methylated by methyltransferases DNMT1, DNMT 3a, and DNMT 3b (which block promoter gene regions to be silenced). (B) Methylated CpGs then attach to methyl-binding proteins (containing methyl-binding domains) “MBDPs” which then recruit diverse transcription repression complexes containing histone modification constriction elements and enzymes such as HDACs and HKMTs. (C) Diverse histone modification enzymes can directly alter histone H3 and H4 tails (tetramers) of the histone unit that corresponds to complementary influences by nucleosomal ATPase reposition machinery containing chromodomains or bromodomains. (D) For gene expression, nucleosomal reposition elements destabilize H2 cores and mobilize nucleosomes through core variant exchange, which initiate nucleosomal ejection, histone H1 linker loss of integrity by several high mobility group proteins (HMG) and a loss of DNA–histone affinity near transcription start sites. In contrast, gene silencing requires H2 core stable variant exchange and recruitment of constrictive nucleosomal remoding complexes, thereby creating mechanical blockage near transcription start sites. (E) Silencing elements are brought together by heterochromatin proteins HP1 α,β which adjoins a number of silencing components in heterochromatin ranging from methylated CpGs, DNMTs, repression complexes such as MBD1-SETDB1-CAF1, silencing marks such as H3K9me3, and nucleosomal reposition machinery. These collective effects reinforce compression of nucleosomes close to the methylated DNA to ensure silencing, when silent heterochromatin is located throughout the lamina circumscribing the nuclear envelope.

Fig. 2

The epigenome is flexible, most impressionable during prenatal and early developmental periods, impacted by environment, replicated through mitosis and can yield long-lasting phenotypic effects that remain stable through adulthood. Adverse impact on epigenetic development can yield maladaptive phenotypic consequences, potentially contributing greater risk of developing adult-onset disease in offspring and subsequent progeny.