Epigenetics At A Glance
Just recently, scientists have discovered four additional bases. These new bases are much like the other DNA bases (cytosine, guanine, thymine, and adenosine) but are all derivatives of cytosine. The 5th and 6th bases are cytosine with an addition of a methyl group. These bases cause the DNA double helix to coil tighter than regular cytosine does, resulting in the silencing of genes. The 7th and 8th bases are versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming (38). These bases sometimes replace cytosine. in the make-up and transcription of DNA. This discovery could advance stem cell research by allowing researcheres to better understand DNA changes, such as the removal of chemical groups through demethylation, which could then be used to reprogram adult cells to act like stem cells. It could also give scientists the opportunity to reactivate suppressor genes that had been silenced by DNA methylation (38).
Cytosine, the 5th base Methylcytosine, and the 6th base, Hydroxymethylcytosine
5th, 6th, 7th, and 8th Bases
Nutrients from our food group are turned into methyl groups along a pathway. The pathway is made up of many players that manipulate molecules into methyl groups and ultimately put them on our DNA. (5)
To prove that diet does affect epigenetic mechanisms, alot of labs are done on mice because humans are genetically different, have even more different epigenomes making it hard to not only regulate what they eat but if the effects are the same from person to person.
Below is a chart on nutrients that affect our epigenome and where they come from. (5)
Diet
Epigenetic Mechanisms
RNA-Associated Silencing is the supression of genes by RNA when it is in the form of noncoding or interference RNA. When RNA is in the form of RNA interference, it participates in post transcriptional and transcriptional silencing of the genes by destroying mRNA, keeping them from carrying genetic information from the DNA to the ribosomes (37). Noncoding RNA contributes to the establishment of chromatin structure and maintains epigenetic memory. In the transcription process of RNA, noncoding RNA targets transcriptional activators or repressors that control the gene's expression (36). In both forms of RNA, heterochromatin can form. Heterochromatin is chromosome material that has a greater density than normal that can suppresses or modifies genes which affects the gene expression. RNA can also trigger histone modifications and DNA methylation (27).
As we age, our stem cells divide more and more to replenish tissue damage. The cells in the tissues' life span is only a couple of weeks, maybe months. Then they need to be replenished again. If they divide more than a given number of times, these epigenetic patterns will show subtle shifts that increase with age.
Ageing
Chemicals and additives that enter our bodies can also affect the epigenome. Bisphenol A (BPA), a compound used to make polycarbonate plastic, is used in many consumer products including water bottles and tin cans. When pregnant yellow aguoti mothers were fed BPA, more yellow, unhealthy babies were born than normal. Exposure to BPA during during early development had caused decreased methylation of the agouti gene.
Exposure to Environmental Chemical, Drugs, or Pharmaceuticals
A mother's diet during pregnancy and what the infant is fed can cause changes that stick with the child into adulthood. Animal studies have shown that defiency of methyl-donating folate or chlorine during late fetal or early postnatal development causes certain regions of the genome to be under methylated for life. For adults, a methyl deficient diet still leads to a decrease in DNA methylation, but the changes can be reversed by consuming a normal diet.
Development
Factors That Affect Epigenetic Mechanisms
A visual aid showing a brief summary of what happens to noncoding RNA compared to normal RNA
DNA Methylation is the addition of a methyl group to the C5 position of the cytosine at a CpG site. CpG sites are the spots in the genome where a guanine follows a cytosine (34). This addition can either activate or repress genes. Repetitive, non-coding sequences are more methylated while sequences with more CpG sites are barely methylated. The more methylation in a sequence, the more likely supressed the gene is as the presence of a methyl group prevents transcription factors from functioning, blocking the transcription (34). Methylation is present in regulating cellular processes such as the division of somatic cells, inactivation of the X-chromosome, genomic imprinting and gene transcription. It does not affect the genetic code, but instead the epigenetic code.
Histone Modification is the binding of epigenetic factors to histone tails. Histones are proteins that make up the core of the nucleosomes, which is a small part in the chromatin structure. The binding of epigenetic factors to the histone tails can alter the extent to which DNA is wrapped around the histones. The extent to which the histones interact with the DNA in the nucleosomes determine the condition of the chromatin. The form of the chromatin affects the availability of selected genes that can be activated or result in abnormal genes (35).
The modifications of histones can change expression of genes in two ways:
1. The histones and DNA interact differently resulting in the the chromatin to coil incorrectly.
2. The altered histones send signals for the nonhistone proteins which then alter the chromatin. (39)
On the left, the tails of histone proteins bind DNA in chromatin. On the other side the tails let go, allowing the DNA strands to be read for gene transcription.
Location of a methyl group once it attaches itself onto Cytosine. This forms 5-Methylcytosine, also known as the 5th DNA base.
How It Works
Epigenetic modifications affect genes through "marks", chemical additions to the genetic sequence. These groups change the structure and appearance of DNA, altering how a gene interacts with transcribing molecules in the cell's nucleus (41). This can result in whether a gene produces protein or not. Mutations, insertions, and deletions in the DNA sequence may also affect the sequence of the protein. For example, mutations in the DNA sequence can prevent a gene from being recognized as a gene, resulting in the gene being turned off.
There are different kinds of epigenetic "marks". The addition of methyl groups to the DNA backbone, for example, is used on some genes to distinguish the gene copy inherited from the father and that inherited from the mother (41). Known as imprinting, the marks distinguish the gene copies and tell the cell which copy it needs to produce proteins.