The electrodynamic electromagnetic field interactions, and complexities are quantum field biological interactions and when applicable to physiology are under involuntary subconscious control, the quantum field biological interactions have effect within all organic interactions, and therefore all epigenetic modifications; It would be reasonable to say that all interactions conform to 'natures universal rules' of quantum field electromagnetism as electrons and protons tunnel akin to waves through the DNA and enzymatic molecule structures.
Hypothesis:
The combination of electron spin and quantum field electromagnetism is so highly sensitive, the act of thought (pseudocertainty) can modify the quantum field spin of a quark or electron via subconscious electromagnetism (King.JL(2021)) laboratory experimentation will prove this Hypothesis; in a similar way to the measurement that modifies the Quarks and electron spin under laboratory conditions, as proven with quantum bitcoin encrypted keys. Quantum bitcoin encryption keys utilize the spin of quantum entangled electron field and the act of measurement via the orientation of the electron spin indicates a 1 or 0; thus, the act of measurement modifies the electron spin to a 1 (up) or 0 (down) status, depending on the initial transmitted electron spin state. Bitcoin quantum entangled encryption keys are considered safer for bank transactions as they do not completely rely on classical programming.
“thought is equal to energy internal to human physiology” (King.J.L(1991)) via quantum entanglement, especially with respect to neurology. Neurologically, the sodium and potassium perpetuate the field electromagnetic electrodynamic fields via quantum field biological interactions thus, the electromagnetic chemical transmissions perpetuate (see figure 1e - Feynman diagram) along the nerve fiber (axon) to the synaptic gaps for cerebellum fluid enzymic interactions of which conform to quantum field theory. The above-mentioned quantum field biological interactions are influenced via functional foods, Bio-functional-foods and positive intellectual attitude, effecting epigenetic modifications and therefore immunity which are under involuntary subconscious control. Thus, a conscious positive intellectual attitude has effect of epigenetic enhancement via the subconscious and resultant correct gene expression towards optimum health, though positive or pseudocertainty alone will not achieve optimal healthy ageing in the absence of proper nutrition and exercise.
Telomeres are age related effectors with respect to quantitative cellular replication, and therefore ageing and biological DNA repair system. Each time cell division occurs, the telomeres 'tips' at the end of chromosome diminish as nucleotides erode of the DNA structure and the telomere shortens each cell division, approximately hundred nucleotide telomere repeats must be at the end of chromosome to avoid activation of the biological DNA repair pathways; researchers at Stanford University have developed a new procedure to lengthen chromosomal telomeres, effectively quantitatively increasing cellular division by preventing shortening of the chromosomal 'tips' and extending the biological clock of cellular ageing process; Also Astragalus root have been studied as possible telomerase activators such an extract is TA-65 and vitamin D3 (fish oils) have similar effects of biological clock extension via telomere extension.
The “flow-FISH” test stands for flow cytometry and fluorescence in situ hybridization, that specifically measures the telomere length via blood sample, the flow-FISH test was developed by Canadian researcher Lansdorp, P., (2006) M.D.,Ph. Stress can diminish telomerase activities thereby shortening the biological clock, the opposite is true for individuals with high telomerase of which adds telomeres thereby extension of biological age via extension of quantitative cellular life, with additional telomeres towards optimal health and healthy ageing (or anti-ageing).
Chapter 4
Future of epigenetics and synthetic biology.......................................................52
Biomarker methods of measurement.................................................................53
Future of epigenetics and synthetic biology
The future for epigenetics is further developments in epigenomics and progression of nutrition via enhanced functional foods and Bio-functional foods. Developments toxicology, epidemiology and DoHAD transgenerational among other technological advancement for methods for hydroxy methylation.
SIRT1 and p53... and the progression of histone technological advancement i.e., improved DNA sensitivity for TAB sequential LC-MS also 5hmC marks and other, including SIRT1, NAD+ Trans-Resveratrol for anti-ageing or biological age reversal (Dr D. Sinclair. 2021), also further research with Yamanaker factors (Oct3/4, Sox2, Klf4 ...).
Future advancements of direct detection for 5mC and 5hmC marks is expected, together with detailed understanding of serotonergic marks of serotonlyation. The hormonal functionality of Serotonylation is specific, such as 5-HT in haemostasis and thrombosis is important to possibly prevent and treat haemorrhagic and cardiovascular disorders and beneficial activities with respect to pulmonary hypertension. when large amounts of protein-bound serotonin are found in the blood this suggests the presence of unidentified other serotonylation interactions, suggestive that further research would reveal further proteins, signaling pathways, cellular processes, diseases of serotonylation involvement this is important and necessary research (Also see Appendix I).
Future advancements in the research specializations of Epigenetic Drift, Germ lineage exposures, single cell epigenetics research will occur as further pioneer technological advancements such as Genome Compilers; Computer simulation of various species, including humans these are controversial advancements in computational epigenetics and synthetic biology have been exponential; the technology has evolved and continues to evolve and evoke bioethics with respect to application of DNA and epigenetic programmable applications.
Future of computational synthetic biology for personalized health will become more refined with possible impacts on the production of Bio-Functional-foods that are grown from genetically modified bacteria resulting in grown functional foods with bioactive enhancements. Synthetic biology shall have impacts in the long-term future as human genome, perhaps encourage population genomic and epigenetic drift though very much in the long-term future. Epigenetic Clocks for Anti-ageing Treatments, Personalized synthetic biology will be a significant tool for both gene correction utilising CRISPR system (Cas9 enzyme) and epigenetic modification enhancement providing future Personalized synthetic biology and in the long-term future designer babies utilising Genome Compilers and cloning technologies, although bioethics are and will be considerations.
The first transcriptional methods where expression microarrays are of oligonucleotides which are complementary to transcripts whereby fluorescence labelled complementary DNA (cDNA) is generated from RNA and hybridized utilized for transcriptional profiling.
Next generation sequencing data and heterogeneous technology, improving detection of low-level and divers’ genetic variations, including single nucleotide variants and complex insertions, deletions, duplications or even inversions. This genomic approach has enabled genetic variants to be studied e.g., genome-wide scans Single nucleotide polymorphisms (SNPs) to identify previous unknown genetic variants that modify nutritional response.
SNP-array based genome typing can offers: WetLab, primary analysis, secondary analysis, tertiary analysis, visualization, nucleic acid extraction and purification library preparations, sequencing, De-multiplexing-based calling, read mapping variant calling, variant annotation variant filtering, and integrative genomics viewer (see Appendix III)
Transcriptomics is utilized to analyze a complete set of RNA transcripts expressed via a cell at specific instance, requires array based high-throughput microarray-based method analysis (or RNA-seq.) identifies the RNA profile using NGS technology. RNA-seq has evolved and is widely used tool in Transcriptomics for RNA or non-coding-RNA profiling. The main advantages of RNA-seq are discovery and quantitative measurements combination is possible, whereas strand-specific protocols are adopted. Sequencing depth or library size results with more quantitative precision though 'transcriptional noise' may occur. SNP-array based Genotyping data have been important for genomic wide association studies and the arrival of affordable NGS technology, one million SNPs of SNP arrays have been replaced via the entire genomic sequence of three billion nucleotides that challenged bioinformatics with reference to data storage, quality control and analyst. Both nutrigenetic and nutrigenomic studies may require a systems biology approach to interpret the dynamic microbial community. With a increasing the need for validated sets of bioinformatics tools for the acquisition, management, storage, and retrieval of high-throughput datasets, and for important steps of quality control and analysis.
Patterns of Nutrient/Epigenetic mechanisms of metabolisms
Kev:
DXMTs - DNA methyltransferase
5' MTHF -Methlytetrahydrofolate
Fas
Carbohydrates
Protiens
Hey - circulating homocy steine jhdniaa. jrnjCs - regulators in spermatogenesis
OGT - O-GlcNacylation
SAH - S-adenosylhomocysteine
SAM - S-adenosylmethionine
Fatty Acids")
Glucose
SIRT - sirtuins
TETs - Ten - ele\ en translocatios
THF - Tetrahydrofolate
PRMT - Protem arginine methyltransferases
Pruvate
p-Onda:ior.
[ Amono Acids]
Cioline
Selenium
Acetyl-CoA
Complex
Vitamin B,=
Carbohydrates ect
5' MTHF
Vitamin B12
$AH
W F“
Filate i,B9)
cycle
HCV
Methionine
cycle
Metfi one
Krebs Cycle
Folate B9
Ot-Ketoglutarate
z-''
Fe2*
Ascobate
Ct-Ketoglutarate
Histone acetylation
DNA aemethylation
Histone de/methyiation
riiatene 0-Glc..acvlatioti
DriMTs
jhdm2a jmjCs
SIRT
TETs
PRMTs
OGT
Insulin Resistance
Metabolic Signaling Energy Metabilism
Glucose Homeostasis
Lipogeneesis
Sirtuins - (SIRT1 - 7) are protein regulatory genes that has anti-ageing properties by switching on longevity genes among other functionalities.
1 - AceCS-1 (acetyl-CoA synthetase) - utilizes Acetyl coenzyme Acetl-coA enzyme of the Krebs-cycle for fatty acid and lipid biosynthesis.
The SIRT1 protein has interactions with NAD+ functionality within nucleic and epithelial cytoplasmic interactions in the heart, liver, skeletal muscles and autophagy (see 1-9).
2 - eNOS - endothelial nitric oxide is a central homeostatic regulator - expression is stimulated via trans-resveratrol that is found in red-grape-skin and Japanese-not-weed -associated with retinal nutrient
4 - P53 is a tumor suppressor protein that represses SIRT1 via apoptosis through transcriptional regulation of Autophagy, Senescence, Apoptosis. P53 is also a Biomarker
5 - PGC-1a is transcription coactivator, mitochondrial biogenesis and also cytoplasmic metabolism, Inflammation and Oxidative Stress.
6-FOXOs - the transcription factor is acetylated in response to stress deacetylation promotes activity in cell cycle inhibition and resistance to oxidative stress. CBP/p300, stimulates its pro-apoptotic activity, both p53dependent or p53-independent.
7-CRTC2 - transducers of regulated cAMP (calcium metabolism) response binding protein of transcription
delivery and functionality in the heart and skeletal muscles.
coactivators, these proteins promote transcriptional cAMP response binding protein of phosphorylated AMP-activated protein kinase sequestered in the liver. | ||
3 - Atgs - Autophagy-related gene or autophagocytosis functionality of lysosome, Yoshinori Ohsum deduced the mechanisms of autophagy during 2016, refers to Cellular degradation. |
8 - SREBP-1 (sterol regulatory element-binding protein 1 ) is associated with lipogenesis via the insulin stimulated SREBP-1c that enhances glycolysis located in the liver on chromosome 17 | |
9 - LXR - digestive anabolic Liver X Receptors |
Quick Reference Guide to Histone Modifications
Table 10 - shows the most common histone modifications: - | |||
Histone modification or biomarkers see Appendix III |
Functional Location (Ac, Me, P, or Ub) see fugue 1e |
Location of histone modification |
Marker association |
H3K4me1 |
Activation |
Promoters | |
H3K4me3 |
Activation |
Gene bodies | |
H3K36me3 |
Activation |
Gene bodies | |
H3K79me2 |
Activation |
enhancers, promoters | |
H3K9Ac |
Activation |
enhancers, promoters | |
H3K4me2 |
Activation |
enhancers, promoters |
Embryonic development epigenetic memory |
H3K27Ac |
Activation |
enhancers, promoters | |
H4K16Ac |
Activation |
Biological Repetitive sequences | |
H3K27me3 |
Repression |
Promoters, gene rich regions |
Embryonic development epigenetic memory |
H3K9me3 |
Repression |
Biological repeats, telomeres, per centromeres | |
Gamma H2A.X |
DNA replication DNA double strand breaks | ||
H3S10P |
DNA replication |
Mitotic chromosomes |
Appendix III
Computational gene mapping and biomarkers
Appendix III shows an example of computational gene mapping showing gene biomarkers or SNPs, researchers have found SNPs may help predict an individual's response to certain drugs, susceptibility to environmental factors such as toxins,
Scale
chrX:
15,565,000| 15,570,000| 15,575,000| 15,580.000| 15,585,000| 15,590.000| 15,595.000| 15.600,000|
Alt Haplotypes
Reference Assembly Fix Patch Sequence Alignments
Reference Assembly Alternate Haplotype Sequence Alignm
ACE2
ACE2«
ACE2
ACE2
AC097625.1
RefSeq Curated
OMIM Alleles
ACE2
ENCODE cCREs
Layered H3K27Ac
Cons 100 Verts
Rhesus
Meuse
Elephant
Chicken
XJropicalis
Zebrafish
Common dbSNP(153)
RepeatMasker
GENCODE V36 (3 items filtered)
RefSeq genes from NCBI
OMIM Allelic Variant
Phenotypes
Gene Expression in 54 tissues from GTEx RNA-seq of 17382 samples, 948 donors (V8. Aug 2019)
ENCODE Candidate Cis-Regulatory Elements (cCREs) combined from all cell types
H3K27Ac Mark (Often Found Near Regulatory Elements) on 7 cell lines from ENCODE
100 vertebrates Basewise Conservation
Multiz Alignments of 100 Vertebrates
Short Genetic Variants from dbSNP release
Repeating Elements
latMasker
GSl -594A7.31
GS1-594A7.3
and risk of developing particular diseases. SNPs can also be used to track the inheritance of disease genes within families. SNPs may help predict an individual's response to certain drug types and susceptibility to environmental factors such as toxins, and the risk of developing particular
diseases. SNPs can also be used to track the inheritance of disease gene
biomarkers within families though epigenetics is dynamic thus inheritance is not always applicable due to systems of biological age reversal.
Bio-Functional-foods are grown from genetically modified bacteria, fungi and algae - utilising synthetic biology
Re: to feed populations after/during droughts or floods and supermarket supplies
This was posted to the Botswana government and Whitehouse and Chinese government re: to feed global populations after or during droughts or floods.
Functional foods are foods grown from bacteria, fungi and algae (utilising synthetic biology); grown under laboratory conditions on an industrial scale. The functional foods should contain, NAD+, Sirtuins, trans-resveratrol, protein, minerals, vitamins and other health beneficial ingredients. The tofu-like-jelly-blocks of functional foods would be in different colours to represent different nutrients that have both nutritional and health benefits, perhaps complement or replacement of fruit and vegetables due to long shelf-life (1 year); also, to feed populations after/during droughts or floods and dessert environments.
I have written a book: nutrition, functional foods and epigenetics and shall publish in the future.
John Lawrence king
Appendix IV Epigenetic resources
There are more than 100 papers per year on histone methylation and acetylation and plenty of internet resources: -
IHEC - international Human epigenome Consortium - HEC Data Portal IHE makes available comprehensive sets of reference epigenomics relevant to health and disease via data portal- http://ihec-epigenome s.org/ the objectives of the Assay Standards Working Group is twofold: to define the assays required for three distinct classes of reference epigenome, and to define standardized protocols and quality control metrics for each assay.
UCSC - epigenome project - https://www.genome.ucsc.edu On June 22, 2000, UCSC and the other members of the International Human Genome Project consortium completed the first working draft of the human genome assembly, forever ensuring free public access.
The following tools and utilities created by outside groups may be helpful: (a) BEDOPS - A highly scalable and easily parallelizable genome analysis tools - A selection of tools for a wide-range of genomics analysis tasks
(b) bwtool - A command-line utility for bigWig files
(c) CrossMap - A program for genome coordinate conversion between different assemblies
(d) CruzDb - Python package to load genome annotations from our servers
(e) libBigWig - A C library to read bigWig files, without a dependency on our source code
(f) MakeHub - Python tool to build assembly hub files for new genomes
(g) RTracklayer - R package to import genome annotations from our databases
(h) trackhub - Python package to manage files in our trackDb format
(i) twobitreader - Python package to open 2bit genome sequence files
(j) ucsc-genomes-download - Python package to download genome sequences from our servers
(k) WiggleTools - C++ Unix command-line tool to work with bigWig files: combine, merge, scale, aggregate and many other operations
Deep blue - epigenetic data server - deepblue.mpi-inf.mpg.de/ The DeepBlue
Epigenomic Data Server provides a central data access hub for large collections of epigenomic data. It organizes the data from different sources using controlled vocabularies and ontologies. The data is stored in our server, where the users can access the data programmatically or by our web interface
Epigenie — informally informative — https://epigenie.com, Epigenetic regulatory cascades can be complex affairs...a recent chromatin effector self-regulatory organisation.
Toolbox Genomics kits - test that shows epigenetic health-toolbox Genomics -DNA Test Kits & Panels For Licensed ...www.32andMe.com... https://www. toolboxgenomics. com a variety of DNA tests for clients, with different options for both licensed healthcare practitioners as well as other health & wellness professionals.
Science Journals available on epigenetics: -
> epigeneticsepigenomics
> environmental epigenetics
> clinical epigeneticsepigenetics insightsepigenetics and chromatinepigenetics and
epigenomics...
> this list would be infinite with YouTube as approaching 2021 +
References and further internet research:
Bing video
and antitumor
^ sheeky science - SIRT1 go down in ageing & senescence? -https://www.bing.com/videos/search p53 - Bing images https://www.bing.com
PGC-1a, Inflammation, and Oxidative Stress: An Integrative View in Metabolism https://www.hindawi.com/journals/omd/2020/1452696/
Enforced PGC-1a expression promotes CD8 T cell fitness, memory formation immunity lxr- anabolism - Bing images https://www.bing.com/images/search? Cellular & Molecular Immunology (www.nature.com) www.researchgate.net www.abcam.com Functional Nutrition Alliance
• 5-hmC - 5-Hvdroxvmethvlcvtosine (see Ten-eleven transferase (TET) enzymes)
• 5-mC - 5-Methvlcvtosine (see Ten-eleven transferase (TET) enzymes)
• 5' MTHF -MethlYtetrahYdrofolate - active folic acid, involved in serotonin and methionine production and also DNA synthesis.
• Acetylation - influence transcriptional regulation and expression with lysine residues, describes a reaction that inserts an acetyl functional group into a biological compound. The opposite biological reaction is called deacetylation that removes the acetyl group. Acetylation can alter gene expression epigenetically.
• A utophagy - replenishment of cells (degradation) for heather cells.
• Crotonylation is a reversible modification via crotonyl transferases (writers) and decrotonylases (erasers). Crotonylation has overlapped acyl-transferases and de-acylases with acetylation and other types of histone acylations at site 25, 30 and also overlapped modification sites on histones at 29, 31. additional epigenetic modification on histones, crotonylation also occurs in histone proteins 25, 26, 27, 28 and participates metabolic pathways such as acetylation 29 on the histone complex. These findings suggest that crotonylation is a global PTM with a complex interplay with other acylations Lysine crotonylation on histones is a recently identified post-translational modification and been demonstrated to associate with active promoters to directly stimulate transcription.
• Citrullination - citrullination is a novel arginine-directed post-translational modification resultant in permanent change in the referenced protein. Peptidyl arginine deiminases mediate calcium-dependent deamination of the guanidino group of arginine side chains. Citrullination is a facilitator modifying known “self-antigens” to foreign, unrecognized proteins, vulnerable immunity. Citrullination is a general regulatory mechanism that occurs during apoptosis; Citrullination is also part of normal physiology, for example, citrullination of trichohyalin in the hair follicle, myelin basic protein, histones in the nucleus, and keratin in the nails and skin.
• Chromosomes are comprised of chromatins (see histones, octamers, nucleosome and DNA)
• CRISPR/Cas9 is a system for gene editing, utilising Cas9 bacterial enzyme that utilizes a guide RNA molecule to find and modify specific nucleotide sequences in the eukaryotic genome.
• DADS - Diallyl Disulfide and Allyl Nercaptan (AN) are both inhibitors of HDAC activity (see HDAC)
• Demethylation is a pathway resultant in the removal of a methyl molecular group (CH3), most demethylation results in the replacement of a methyl group by a hydrogen atom, with a loss of one carbon and two hydrogen atoms, the counterpart of demethylation is methylation.
• DNMTs - DNA methyltransferase - family of enzymes that regulate epigenetic affiliates.
• Genome Compiler or DNA compiler - is an all-in-one platform for genetic engineering and synthetic biology provides a set of comprehensive tools for DNA design and visualization, and a seamless DNA ordering via all-in-one software. The Materials Box inside DNA compiler consists of sequences from Addgene, Sigma Aldrich, Synberc, Lucigen, iGEM, Plasmapper; it is possible to query the NCBI database from within and instantly import your data into the Materials Box directly from DNA Compiler and post the compiled product to an organization for production of the complied genomic, bacteria or fungi basted product.
• DNA is a negatively charged helical structure due to the phosphate groups in its phosphate-sugar backbone, an octamer histone complex coil up tightly to form nucleosome, as the sum of nucleosol histone complexes is positively charged proteins that adhere to negatively-charged DNA and form complexes called nucleosomes.
• DNA methylation (CpG and non-CpG) - gene sequencing that is enriched at CpG (a methyl group (CH-) is introduced); an additional methyl groups is component of bases of DNA (see methylation)
• Electron - An electron is a negatively charged (though sometime positive called a cation subatomic particle. Electrons can be either free or bound to the nucleus of an atom. Electrons spherical shells the represent energy levels; the charge on a single electron is considered as the unit electrical charge.
• Epigenome epigenomics is the analysis of genome-wide consequences of epigenetic modifications across many genes in cells or entire organism. The Human Epigenome/Genome Project is an international collaboration ‘to identify, catalogue and interpret genome-wide epigenetic methylation patterns of all human genes.
• Epigenetic Drift - the genomic sequence does not change over time, however, epigenetic marks, and methylation are variable histone modifications underlying gene expression and control differentiates cell types, the epigenetic patterns are established early in development. There is a highly developed mathematical theory of how quasi-neutral mutations may behave in populations.
• Epigenetic regulation - of transcription comprises of three - Histone modifications, DNA methylation, and non-coding RNA.
• Epigenetics project road map - shows chromatin computational maps in the UCSC genome project browser - indicates RNA transcription gene cluster(mark) showing states and events of different tissue types.
• Epigenetics - The study of heritable meiotic and/or miotic changes in gene expression and/or repression functionalities that are not resultant of changes in DNA sequence; subtle chemical changes such as methylation of the nucleotide cytosine in gene promoter sequences or acetylation of the histone proteins with which DNA is structurally associated.; or: heritable stabilized phenotype of structural chromosomal modifications effecting histone octamer complex methylation and acetylation involved in tissue specific
patterns t- hat register and signal heritable gene expression without
sequential DNA modifications. gH2AX assay Phosphorylated gH2AX is a protein that accumulates at epigenetic sites that is detected by fluorescent antibodies, used to determine the amount of chromosomal strand breaks within a nucleus.
• Gene locus is the specific physical location of a gene or DNA sequence on a chromosome, the plural of locus is - loci
• Genome - total genetic material within a biological cell or system.
• GIcNAcylation - O-GlcNAcylation is the attachment of O-linked N-acetyl glucosamine (O-GlcNAc) moieties to cytoplasmic nuclear mitochondrial proteins is a regulatory post-translational modification, that involves cytoplasmic cellular processes with nuclear proteins and addition of OGlcNAc to proteins that are catalyzed by O-GlcNAc transferase, and its removal is catalyzed by O-GlcNAc-selective N-acetyl-fi-dglucosaminidase.
• HAT - Histone acetyltransferases catalyze the transfer of an acetyl group from acetyl coenzyme A, while histone deacetylases (HDAC) perform the antagonistic state of removing the acetyl group. Histone acetylation has an important role in the modulation of chromatin condensation and transcriptional regulation.
• HDAC are enzymes which remove acetyl groups from lysine residues in the tail region of histone/octamer complexes or nucleosomes. Through this mechanism, HDAC are involved in the modification of chromatin architecture and govern the repression of oncogenes, tumor suppressors, and inflammatory genes (de Ruijter et al., 2003), garlic contains 40-60% DADS (Diallyl Disulfide).
• Histones - are family of small positively charged proteins (amino acid residues such as lysine and arginine) are termed H1, H2A, H2B, H3, and H4 (Van Holde, 1988) that form an octameter, with linker proteins making a nucleosome involved in regulation...
• Histone-tail modifications - Histone-tail modifications are transactional epigenetics that undergo events via - acetylation, phosphorylation, or methylation, these three are necessary to allow the activity of the chromatin remodeling complex. Methylation activates or represses gene expression depending on which residue is methylated; Methylation of histone methyltransferases (HMTs), of Lysine SET domain containing (histone tails) and Non-SET domain containing (histone core octamer)
• Histone acetylation - occurs on the e-amino lysine residue and promotes DNA unfolding - CoA (acetyl coenzyme A) and lysine where HAT (histone acetyltransferase enzyme, inhibits gene expression - i.e. repression for immunological defense) and HDAC (histone deacetylase enzyme, HDAC enables nucleic gene expression), n-butyrate is a HDAC inhibitor where HATs are co-activators during transcription. HATs categories are: GCN5, MYST(MOZ), P300/CBP and SRC/p160 of the nuclear receptor co-activator family. Histone and non-histone proteins are catalyzed via HATs. Reversible histone acetylation catalyzed via HATs and HDATs also histone acetylation can inhibit H1-mediated salt insolubility assisting salt solubility concentrations that effects binding and relaxation of DNA coils on the nucleosomal structure. Thus, HATS and HDAC are involved in control gene expression switching gene expression off or on. This effect is consistent with the expected large reduction in electron density on the amino nitrogen upon acetylation thus, making coordination with the coenzyme copper much less strong; the structure of histones shows the patterns of histone acetylation and DNA methylation are quite precise and important mechanisms for epigenetic alteration of gene expression. (See acetylation, HATs, HDAC, histone methylation and figure 1a, 1b and figure 1d).
• Hcy - circulating homocysteine - high levels in the blood are undesirable due to coagulation.
• Histone methylation cause local formation of chromatin, which is reversible also can activate or suppress gene expression in accordance to different lysine dependent states (i.e. Mono-methyl, Di-methyl, or Trimethyl (binds the DNA coils around the octamers); The demethylated function is in reverse releasing the DNA coils during transcription. There are seven transcriptional regulatory core histone modifications on the 3 histone-tail that is:- 2 active promoters (H3K9ac, H3K4me3), 2 enhancer promoters (H3K4me1 (stem cell line), H3K27ac), 1 transcribed gene bodies (H3K36me3), 1 polycomb promoters(H3K27me3), 1 heterochromatin (H3K9me3) it is possible to define chromatin profile states(marks) of the genome via the seven histone-tail modification marker state (see acetylation, histone acetylation, HATs,
HDAC, and figure 1a, 1b and figure 1d) Histone modifications - mark transcriptional events that are ether - active, repressed, or poised states (see figure 1d).
• Isomerization - Isomerism definition is compounds which have same molecular formula but differ in reverse arrangement of atoms known as isomers classification of isomerism. There are two main types of isomerism: - structural isomerism and stereoisomerism.
• Immunity - The ability of an organism to resist a particular infection or toxin by the action of specific antibodies or hypersensitive white blood cells.
• Lysine methylation - enable transcriptional regulatory binding sites for core histone modificatory co-activators on histone tails (see histone methylation).
• Methylation - A chemical reaction in which a methyl group (CH-) is introduced in a molecule. A particular example is the replacement of a hydrogen atom by a methyl group DNA methylation is a common molecular alteration in colorectal cancer cells.
• Microbiota - (microfauna and microflora) The smallest organisms, comprising Bacteria, Fungi, and algae. Microbiota are found in the lungs, stomach, intestinal tract and colon.
• Neutron consist of 1 up quark and 2 down quarks. Also, an elementary particle that has no charge, with a mass slightly greater than that of a proton, and spin of a A, a component of the nuclei of all atoms except those of hydrogen (see quark & protons).
• Nucleosome core complex is made from an octamer that is a eight histone protein complex, at the center of a nucleosome consists of two copies of the four core histone proteins (H2A, H2B, H3 and H4), involved in chromatin folding and co-factor recruitment (see figure 1a, 1b, 1d).
• OGT - O-GlcNacylation - enzymic post-translational regulator with TET2 interactions to produce hydroxy methyl cytosine regulating transcription.
• Phenotype is the total physical gene expression, different genotypes may result from different Phenotype, mutations can cause changes in phenotype.
• Positive intellectual attitude - an approach that can be advantageous towards optimal health, i.e., healthy-lifestyle-choices towards exercise and intake of healthy nutrition (also see figure 1c - Feynman diagram and Quantum field biological interactions and functional foods on epigenetics).
• Phosphorylation - is a biochemical process that involves addition of phosphate to an organic compound. Examples are the addition of phosphate to glucose producing glucose monophosphate with addition of phosphate to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP). Phosphorylation is carried out utilising the enzyme phosphotransferases or kinases. Phosphorylated gH2AX is a protein that accumulates at sites of DNA breaks, detection via fluorescent antibodies that is used to determine the quantity of DNA strand breaks within a nucleus Phosphorylation regulates ubiquitylation.
• PRMT - Protein arginine methyltransferases - mediate protein(s) substrate methylation of arginine residues, involved in T-lymphocyte activation and gluconeogenesis.
• Proton - a proton is a subatomic stable particle with mass defined as positive charge made from three quarks (2 up & 1 down). The atomic number is the number of protons within an atom, the nucleus of every atom contains protons, both protons and neutrons are found in the atom (see quark & neutron).
• Ubiquitylation - (or ubiquitination) is an enzymatic process involves the bonding of a ubiquitin protein to a substrate protein, Ubiquitin contains conserved sequence of 76 amino acids and linked via covalently bonded proteins proteasomes that promotes apoptosis of the cell; the ubiquitous protein proteasomes is present in all eukaryotic cells. Ubiquitylation regulated post-translational modification of proteins of ubiquitin molecule, attached to a lysine amino acid in the Degradation of p53 promoted by E3 ubiquitin ligase ITCH via ubiquitylation at the N-terminal border of SAM (methyl group donor) domain of the p53 [alpha] isoforms; the process of ubiquitination can be reversed through the action of deubiquitinase enzymes, by altering the bond between ubiquitin molecule and substrate protein (see phosphorylation).
• repression - inhibits epigenome gene expression, the epigenome defense mechanism (ability to switch genes off and on) that co-evolved within invertebrates.
• SAM - S-Adenosyl-methionine is a methyl group donor, a substrate that product is SAH.
• SAH - S-adenosylhomocysteine - a protein that has a product of SAH into homocysteine and adenosine.
• SIRT1 - Sirtuins - see Appendix I
• Serotonylation is a receptor independent signaling mechanism, a process for exocytosis of thrombocytes of the blood platelets via serotonlyation of small GTPases such as Rab4 and RhoA. Serotonylation activates of serotonin 5-hydroxytryptamine (that is a neurotransmitter) during intracellular processes that have lasting effects of covalent bonds within enzymes. The enzymes attach to the serotonin on glutamine residues, this signaling mechanism utilizes transglutaminase antibody enzyme for the creation of glutamylamide bonds. Serotonylation is through small GTPases the process by which serotonin controls release of pancreatic insulin from beta cells for the regulation of blood glucose levels. Thus, defects in transglutaminase lead to glucose intolerance, small GTPases are involved, and also regulate vascular aorta smooth muscles. serotonylation modifying proteins are also integral to cytoskeleton via alpha-actin, beta-actin, gamma-actin and myosin heavy chains. Serotonin is also a regulator of mood, appetite, and sleep cognitive functions, memory and learning.
• Small GTPases - are tightly regulated molecular switches that make binary on/off through controlled usage of GTP activation and hydrolysis of GTP to GDP that is inactivation.
• Subconscious is part of the mind that controls involuntary movement and automatic-immunity.....whilst a higher percentage the brain is functioning on alpha waves; the conscious is part of the mind that controls voluntary movement and conscious thoughts, whilst mostly higher percentage functioning on beta waves, though there are other measurable wave frequencies.
• Supersymmetry is an extension of the Standard Model that predicts a partner particle (referred to as anti-matter) for each particle in the Standard Model (see Standard Model)
• Standard Model - a mathematical description of the elementary particles (of fields) of matter and electromagnetic, weak, and strong forces by which they interact (see Supersymmetry).
• Sumoylation, is a post-translational modification that attaches the SUMO protein to intended proteins regulating activity, function, subcellular localization and stability (Sumoylation Inhibits TAK-981)
• Synthetic biology - A scientific field that draws on principles of engineering to create new biological parts, devices, or systems to redesign or improve natural biological systems; The capability to make DNA polymers with specific base sequences that behave as genes. These DNA polymers consist of various small DNA sequences that are programmed together (via amino acid, DNA or protein computational program compilers) by homologous recombination to produce functional genes with required genomic and epigenetic health benefit properties to achieve healthy ageing or age reversal (Synthetic biology is also used with mice, yeast, bacteria and fungi).
• Ten-eleven transferase (TET) enzymes - TET1 or TET2 is found in the embryonic stem cells, while TET3 is found in the stem cells; the TETs are expressed ubiquitously in differentiated cells, (TET1) is a DNA demethylation enzyme associated with tumorigenesis and biological process via catalysis and hydroxylation of DNA ( 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), further catalyze oxidation of 5hmC to 5-formylcytosine (5fC) and then to 5-carboxycytosine (5caC). There are interactions between TET, active DNA demethylation (of DNA base cytosine), transcription, genomic instability, and the DNA damage/repair response.
• Telomeres are protective tips at the ends of chromosomes, during cellular division, the tips shorten and over time, the telomeres become too short to sustain cell division and the cell become senescent. Other influences include age, stress, poor lifestyle choices and exposure to environmental toxins, it is essential to maintain telomere length. Telomerase is naturally occurring enzyme that lengthens telomeres and prevents shortening thereby extending the biological clock with telomere extension therapeutic techniques.
• THF - Tetrahydrofolate - one-carbon group carrier involved in amino and nucleic acid biosynthesis and thymidine precursor in synthetic pathways
• Quark - any of a number of subatomic particles carrying a fractional electric charge, it takes three quarks (1 up 2 down held together by gluons) to make a proton (see proton & neutron).