Histone methylation (Me) causes local formation of heterochromatin, which is reversible also can activate or suppress gene expression in accordance to different lysine dependent states (i.e. Mono-methyl, Di-methyl, or Tri-methyl (binds) states; The de-methylated function is in reverse (relaxes) the histone-tails during transcription. There are seven transcriptional regulatory core histone modifications on the 3 histone-tail that is:- two active promoters (H3K9ac, H3K4me3), two enhancer promoters (H3K4me1 (stem cell line), H3K27ac), one transcribed gene bodies (H3K36me3), one polycomb promoters(H3K27me3), one heterochromatin (H3K9me3) it is possible to define chromatin profile states of the genome via the seven histone-tail modification marker stats (figure 1d, table 10 and see Appendix, I, II).
Table 11 shows Epigenetic Marks and Their Effect on Gene Expression.
Epigenetic mark |
Description |
Effect on gene expression |
Notes |
DNA methylation |
Addition of methyl group to 50 position on pyrimidine ring of cytosine |
Decrease expression |
Effect depends on genomic context. Promoter-associated CpG islands are rarely methylated where as methylation at CpG Island shores is more variable and inversely associated with gene expression. |
DNA hydroxymethylati on |
Placement of hydroxymethyl group on 50 position of pyrimidine ring of cytosine |
Increase expression |
Considered to be a transient mark in the active demethylation process. |
H3K27ac |
Acetylation of lysine 27 on histone 3 |
Increase expression |
Associated with transcriptional initiation in euchromatin. |
H3K9ac |
Acetylation of lysine 9 on histone 3 |
Increase expression |
Associated With transcriptional initiation in euchromatin. |
H4K16ac |
Acetylation of lysine 16 on histone 4 |
Increase expression |
Localized to active genes and enhancer regions. |
H3K27me3 |
Trimethylation of lysine 27 on histone 3 |
Decrease |
Associated with gene repression of inactive developmental loci, placed by polycombrep repressive complex. |
H3K36me3 |
Trimethylation of lysine 36 on histone 3 |
Increase expression |
Co-localizes with RNA polymerase II during elongation. |
H3K4me1/me2/m e3 |
Mono/di/trimethylation of lysine4 on histone 3 |
Increase expression |
During active transcription. |
H3K9me3 |
Trimethylation of lysine 9 on histone 3 |
Decrease expression |
Associated with repressive heterochromatin |
H3K9me1 |
Monomethylation oflysine 9 on histone 3 |
Increase expression |
Associated with accessible chromatin during active transcription. |
H4K20me1 |
Monomethylation oflysine 20 on histone 4 |
Increase expression |
Associated with accessible chromatin during active transcription, catalyzed by PR-Set 7. |
H2AK119Ub1 |
Monoubiquitination of |
A Decrease Catalyzed by | |
lysine 119 on histone 2 |
Bmi1subunit of polycomb repressive complex 1.II. |
Functional foods are bioactive and help to prevent degenerative conditions such as Alzheimer disease, molecular degenerative disease, encephalopathy, arthritis... (list is exhausting) are internal physiological factors that affect genetic(indirectly) and directly epigenetic modifications; caused by the onset of cell senescence/ageing, though effect can be reduced in favor of healthy ageing with appropriate nutrition. Functional foods and Bio-functional-foods also incorporates all micronutrients and microfauna and microflora know as microbiota. Microbiota may be derived from fibrous nutrients together with probiotics in bioyogurt, algae and other functional foods. with adequate fibrosus nutrition, obesity related metabolic diseases may be reduced via the HDAC biological dependent pathways via repression or expression of genes (see figure 1d, and appendixes).
Providing nutritional intake is adequate, Vitamins, minerals, herbal supplements and micronutrients within functional foods will enhance epigenetic modifications and immunity shall function with reduction of toxins and oxidants, i.e. vitamins A, D and green tea are good examples of antioxidants. The nutritional benefits of fresh and functional foods containing multi vitamins, minerals and herbs are beneficial towards optimal health and healthy ageing. Essential Vitamins A, B2, B6, B9, B12, C, D, E, K... and selenium dependent glutathione and other antioxidants i.e... Trans-Resveratrol also the precursor NAD+, sirtuins and other enhancing nutrients together with bio-cultures will assist towards optimal healthy ageing.
Vitamin C is not produced in-vitro to the physiology therefore daily consumption is important. Vitamin C assist with the regulation of collagen synthesis and essential in bone formation, maintenance of healthy gums, and wound healing there has been suggestions for vitamin C treatment as preventative usage for: influenza, upper respiratory tract infections, diabetes, cataracts, glaucoma, macular degeneration, atherosclerosis, stroke, heart disease and even cancer (Traber et al 2011) vitamin C is noted as a co-factor for histone modifications and reduces oxidative stress and also is neuro-protective and cancer chemo preventative (Li, P.et al - 2004).
Polyunsaturated fats are healthy - unsaturated fats and saturated fats refer to the quantity of hydrogen within the lipid structure of the fat, saturated fats comprise of many hydrogen bonds that are less healthy than unsaturated referred to as polyunsaturated fats that are Omiga-3 fatty acids and omiga-6 fatty acids (see table 11). A high fat diet of saturated animal derived fats changes histone-tail modifications in unwanted ways at the gluconeogenic gene loci; Were as the he healthier Omiga-3 polyunsaturated fats intake has a stabilizing effect. Omiga-3 fatty acids are found in Flaxseed oil, evening primrose oil and fish oil that increase D3, D5 and D6 desaturase enzyme activities that have a healthy dietary effect on blood platelets and immunity._
Table 11 shows the difference between omaga-3 and omega-6 fatty acids derived from functional foods:
omega-3 fatty acids | |
Alpha-linoenic acid |
Wild fruit, berries, leafy vegetables, flaxseed (linseed), rapeseed (canola), hempseed, walnuts. |
Syearidonic acid |
Hempseed & animal products |
Eicosapentaenoic acid |
animal products, in particular fish, some traces in algae. |
Docosahexaenoic acid |
animal products, in particular fish, some traces in algae. |
omega-6 1 |
Fatty acids |
Linolenic acid |
Plant foods, sunflower, safflower, sesame seed, corn, soya beans & walnuts |
Gamma-linolenic acid |
Borage, evening primrose, hempseed |
Arachidonic acid |
animal products |
High intake of arachidonic acid metabolically diminishes the uptake of the healthier omega-3 fatty acids thus, plant derivative fatty acids are more desirable.
Iron is essential mineral for enzymic reactions in all organisms; consumption is naturally via cereals, soybeans, lentils, Spinach and other plant micronutrients that aid towards optimal health and healthy ageing. Iron is a metabolic catalytic coenzyme that is stored in the liver, important in hemoglobin for oxygen transportation via the red blood cells. Iron is important in mitochondria for adenosine triphosphate production during aerobic respiration and other metabolic processes. The iron dependent epigenetic enzyme histone acetyltransferase (see figure 1a & b) facilitates opening of the chromatin gene promoter regions of DNA to enable gene expression. Iron is involved with hemoglobin, phagocytotic white blood cells that assist immunity and diminishes oxidative stress among other functionalities such as the epigenetic regulation of gene expression.
The trace element Selenium modulates the DNA repair system that has antiinflammatory effect among other epigenetic processes on DNA methylation; Selenium has an preventive effect with respect to chronic diseases such as muscular dystrophy (Hogue et al - 1958) and other undesirable histone modifications due to selenium deficiency; quite often natural food sources do not incorporate adequate selenium due to nutrient-poor-soils, food supplements are advisable via a reasonable multi vitamin and mineral supplement or some other bio-functional foods that incorporates Selenium.
Garlic incorporates DADS (Diallyl Disulfide) that are inhibitors of HDAC (histone deacetylase enzyme, which enables gene expression), 40-60% Diallyl Disulfide is found in garlic of which is metabolize in the liver to inhibitory Allyl Nercaptan (AN) enzyme garlic lowers cholesterol and inhibits platelet aggregation and helps towards optimal health.
Other functional foods that are bioactive nutrient such as Broccoli, cabbage and kale incorporate Sulforaphane which are endogenous antioxidants that help prevent cancer and other health benefits. Green Tea incorporate flavonoid polyphenols, catechin and eipgalloatechin-3-gallate (EGCG) that are biological effectors; The EGCGs (50-70% in green tea) inhibit HATS (histone acetyltransferase enzyme) that inhibit unhealthy gene expression. It has also been shone that EGCG reduce HDAC activity in prostate cancer via the LNCap cells and PC-3 cells, that's suppression of class 1 histone deacetylases carcinogenesis (Thakur, v.s et al - 2005) Green tea has desirable epigenetic effect due to 50-70% EGCGs (see figure 1c & 1d, and appendixes).
Turmeric incorporates curcumin which is a polyphenolic compound that has epigenetic effect; curcumin is an antioxidant that utilizes acetyl-CoA and is a HAT inhibitor. Turmeric is anti-inflammatory due to the HAT inhibiting p300/CBP and
HDAC activities (see figure 1b, 1c & 1d) of which, induce anti-inflammatory and anticancer effect (Sharma, et al - 2012). Turmeric also has preventive properties for poor intestinal absorption and preventive properties for type two diabetes via improvement of pancreatic beta-cells functionality. Turmeric is derived from the root rhizomes of the species curcuma longa, that is a member of the ginger classification (see personalized functional foods and Bio-functional-foods).
Table 12 shows functional foods and epigenetic activities that have protective effects against cancer and other diseases | ||
Nutrient |
Functional Foods & Source |
Epigenetic Activities |
Methionine |
Sesame seeds, Brazil nuts, fish, peppers, spinach |
SAM synthesis |
Folic Acid |
Leafy vegetables, sunflower seeds, baker’s yeast, liver |
Methionine synthesis |
Vitamin B12 |
Meat, liver, shellfish, milk |
Methionine synthesis |
Vitamin B6 |
Meats, whole grain products, vegetables, nuts |
Methionine synthesis |
Betaine |
Wheat, spinach, shellfish, and sugar beets |
Break down the toxic by products of SaM synthesis |
Resveratrol |
Red wine |
Removes acetyl groups from histones, improving health |
SAM-e (SAM) |
SAM-e (SAM) Popular dietary supplement pill; unstable in food |
Enzymes transfer methyl groups from SAM directly to the DnA |
Choline |
Egg yolks, liver, soy, cooked beef, chicken, veal and turkey |
Methyl donor to SAM |
Genistein |
Soy, soy products |
Increased methylation, cancer prevention, unknown mechanism |
Sulforaphane |
Broccoli |
Increased histone acetylation turning on anti-cancer genes |
Butyrate |
A compound produced in the intestine when dietary fibre is fermented |
Increased histone acetylation turning on ‘protective’ genes, increased lifespan (shown in the lab in flies) |
Diallyl sulphide (DADS) |
Garlic |
Increased histone acetylation turning on anti-cancer genes |
Choi, S.W.; Friso, S. Epigenetics: A New Bridge between Nutrition and Health. Adv. Nutr. 2010, 1,8-16. Fabiani, R.; Minelli, L.; Bertarelli, G.; Bacci, S. A western dietary pattern increases prostate cancer risk: A systematic review and meta-analysis. Nutrients 2016, 8, 626.
Alcohol is a physiological environment factor associated with several diseases due to the cellular toxic effects on many different tissues via acetaldehyde. Acetaldehyde interferes with DNA synthesis and DNA repair system, noted for the underlying effects of lower and upper gastrointestinal tract cancers. Alcohol induces oxidative stress on the liver and other organs, also impairs one-carbon metabolism that regulates availability of methyl groups, resulting in abnormal methyl group transfer thought to the development of various cancers and other associated diseases.
Alcohol has effect on epigenetics via the one-carbon metabolism and DNA methylation that effects gene expressions by modification of the phenotype without alteration of the DNA base sequencing. DNA methylation alters the methyl group of the 5'-carbon of cytosine the occurs at CpG, in dinucleotide sequence in mammalian genome.
DNA methyltransferases (DNMTs) maintains DNMT1 which preserves DNA methylation levels during cellular mitosis. DNMT3A and DNMT3B regulate cytosine methylation sites (BolandM.J.Christman J.K(2009), DNA methylation has a physiological role in normalization of chromosomal imprinting. Thus alcohol interferes with vitamin folate absorption via inhabitation of the one-carbon metabolism directly; folate, a water soluble vitamin B availability is diminish by alcohol intake an intestinal malabsorption thus increased renal excretion due to deficiency of folate or vitamin B9 (Hamid, A. and Kaur, J(2007).
Epigenetic effects of alcohol on the physiology and many associated diseases all occur via mechanisms of DNA methylation and alcohol induced histone modifications on the histone-tail sites, resultant abnormal DNA methylation that has tissue and gene specificity which easily also influenced by diet, age, and genotype in concordance to biomarkers and quantitatively alcohol consumption. Thus, it is reasonable to say alcohol is not advisable (also see appendixes).
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class (methylxan-thine alkaloid - 1,3,7-trimethyl xanthine), and isochemically related to the purine adenine and guanine bases of (DNA) and (RNA). Caffeine is contained in seeds, nuts, and leaves of various plants native, most abundant source of caffeine is the seed of Coffee plants, belonging to the botanical family of Rubiaceae, two main species are Coffee arabica and Coffee canephora Caffeine-containing drinks, coffee, tea, and cola, coffee is most frequently used beverage worldwide; caffeine alleviates drowsiness and improves alertness and is the most widely consumed and quite legal mild stimulant.
Caffeine is absorbed through the gastrointestinal tract and metabolized in the liver by cytochrome P450 1A2 (CYP1A2), with resultant metabolites: paraxanthine, theophylline, and bromine. Caffeine levels appear in the bloodstream within 1545 min, in 1 hour post ingestion of consumption, crossing the blood brain barrier due to its lipid solubility and makes changes in the cerebral fluid via synaptic enzymic activity. Caffeine and metabolites are excreted by the kidneys, and concentrations decrease by 50%-75% within 3-6 hour of consumption.
The main mechanism are adenosine receptor antagonism and secondary effect is inhibition of phosphodiesterase, with accumulation of cyclic AMP and an intensification of the effects of catechol-amines, effects are cognitive response, increased alertness and attention, and in a complex cardiovascular response, increased blood pressure (Tofalo et al., 2016). Many caffeine stimulant effects are mediated by adenosine receptor sub types A1 and A2A, both expressed and differently distributed in human brain, important in sleep-wake regulation (Svenningsson et al., 1997), caffeine acts on the CNS as an adenosine antagonist, though also has effect on substrate metabolism and neuromuscular function (Goldstein et al., 2010).
Figure 1g - shows the interactions of the Circadian Clock, an important part of nutritional regulation.
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Chapter 3
Quantum field biological interactions........................................................................................42
Quantum field biological interactions and Pseudocertainty on epigenetics...............................43
The mechanism of functional foods and positive intellectual attitude on epigenetics is via Quantum field biological interactions (also see figure 1e - Feynman diagram). Figure 1g - Feynman diagram, (there are an infinite number of Feynman diagrams that are graphical representations of equations).
Quantum field biological interactions -The Feynman diagram shows the Electron positron scattering (called the magnetic moment) where two electrons collide to produce a photon T, given by two diagrams that represent two integrals that are electrons, and the intermediate photon is virtual T is a symbol that carries the quantum numbers of the exchange. The electron scattering exchange is qualitatively even, the two electrons colloid, a photon is emitted and T discharges to the other electron fields (P. Richard - Feynman (1918-1988)).
Quote: “In biological molecules the electrons (and all quantum fields) are significant, quantum tunnelling and entanglement occur internal to the physiology” King.J.L(2021); though “molecules do not have spherical symmetry” (Autschach.J., 2021) although perhaps conform to quantum field theory (Prof. Tong.D - YouTube) and super-symmetry.