Epigenetics and Cancer
Introduction:
Cancer is beyond mutations. By definition, epigenetics is the change in gene translation that is caused by alterations not directly due to genetic mutations in the DNA sequence. The 2 main mechanisms are DNA methylation and covalent modification of histones. By methylation, certain molecular tags (methyl groups) bind to a specific sequence of a gene, that results in its disability hence incapable of being translated into its appropriate protein product. These changes affect the cell’s functions leaving its DNA unchanged. Epi is derived from Latin meaning above; hence an epigenetic configuration overlies our genetic predispositions.
DNA methylation and Cancer:
DNA methylation primarily occurs within
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Some of the factors affecting DNA methylation without DNA change are: Aging: Aging results in the hypomethylation of the genome, while CpG islands are hypermethylated often. Diet: Folate and methionine pathways are sources of methyl groups for DNA and histones. Methyl groups can’t be acquired directly without these cycles. Hence, a diet low in folate and methionine ultimately leads to an alteration in DNA methylation. Environment: Many chemicals in nature can induce epigenetic changes. These include arsenic and cadmium. Arsenic for example leads to the hypomethylation of ras gene which codes for the production of ras proteins that help each cell to grow and divide in appropriate times. Cadmium in turn leads to global hypomethylation by inactivating DNMTs.
In discussion of methylation and cancer is the concept of allelic imprinting. Bannister (n.d.), discusses that DNA methylation is an epigenetic factor for allelic imprinting. The concept of allelic imprinting is when only one of the genes is expressed depending on the parental origin. That is due to methylation, a gene “remembers” what allele to express, either the paternal or the maternal allele. Hence, loss of imprinting due to a defect in methylation leads to cancer. To make things clearer, the example of IGF2 (insulin like growth factor 2) is an imprinted gene expressed only by paternal alleles. If no methylation exists
Epigenetics is a study that entails the heritage changes in gene expressions, which includes both the active and the inactive genes; the changes do not involve changes to the underlying DNA sequence. Meaning, it is a change in phenotypes without the differences in genotypes and consequently, affect how the cells read the genes. The epigenetic modification is a natural occurrence but apparently can be influenced by other several factors, including diseases, the environment, and age. Epigenetic changes can result in adverse damages and can end up causing infections such as cancer (Barton et al, 2016). This paper looks at what epigenetics entails, the hidden life of our genes, how food affects genes and how one can elongate life by improving health status.
It may be possible to pass down epigenetic changes to future generations if the changes occur in sperm or egg cells. Most epigenetic changes that occur in sperm and egg cells get erased when the two combine to form a fertilized egg in a process called "reprogramming." This reprogramming allows the cells of the fetus to "start from scratch" and make their own epigenetic changes. However, scientists think that some of the epigenetic changes in parents ' sperm and egg cells may avoid the reprogramming process and make it through to the next generation. If this is true, things like the food a person eats before they conceive could affect their future child. Scientists now think epigenetics can play a role in the development of some cancers. For instance, an epigenetic change that silences a tumor suppressor gene, such as a gene that keeps the growth of the cell in check, could lead to uncontrolled cellular growth. Another example might be an epigenetic change that "turns off" genes that help repair damaged DNA, leading to an increase in DNA damage, which in turn, increases cancer risk. (US, National Institutes of Health)
Epigenetics refers to external modifications to DNA that turn genes on or off. These alterations do not change the DNA sequence, but instead, they affect how cells read genes. One common example of an epigenetic change is DNA methylation. DNA methylation is the addition of a methyl group to part of the DNA molecule which prevents certain genes from being expressed. It should be noted that epigenetics is a fairly new subdivision in genetics and its importance in evolution and heritability is currently being developed and debated (Furrow 2011).
The genome is the complete set of an individual’s inheritable traits or it’s DNA. As a fetus develops, signals are received that cause incremental change in the gene expression patterns. The DNA in our bodies is wrapped around proteins called histone. The histone and DNA are covered in chemical tags. This structure is called an epigenome. The epigenome shapes the structure of the genome. Epigenetic marks are modifications of DNA and histones. The epigenome tightly wraps inactive genes and allows active genes to be more easily accessible. The epigenome adjusts specific genes in response to our changing environment. The programming of neurons through epigenetic mechanisms is critical in neural development. A type of cellular memory is formed when those changes occur. These are epigenetic tags. Each tag records the cell’s experiences on the DNA. This is to help stabilize gene expression. Over time, and with thousands of different experiences, an epigenetic profile forms for each cell type. Each one is unique, with a distinct identity and a specialized function. A flexible epigenome allows us to adjust and learn from our mistakes. The epigenome responds to signals. These signals come from a variety of places. From fetal development to old age, our epigenome is effected by our environmental factors.
Researchers first thought the genes you receive from your parents are set in stone since they are made of a genetic code set in our DNA sequence;however, they are discovering that there is a second layer of structure that combines with DNA to decide whether or not a gene is active or not, called the epigenome. The epigenome consists of the DNA, histones, a protein DNA is wrapped around, and chemical tags. The epigenome alters the genetic code by directing signals. The signals come from the environment, which are reacted upon by epigenetic tags to turn a gene either on or off without affecting the DNA sequence. Certain things from our environment that send signals to epigenetic tags to change our genes in the epigenome includes the following:
The abnormalities in the epigenome such as lower level of methylation. Cancer cell DNA due to low methylation is highly active so it is more likely to be
Epigenetics is a field where advances are being made daily. Epigenetics is defined as “heritable changes in gene expression that occur without a change in DNA sequence,” as stated by Dr. Alan Wolffe. A way in which we can understand this definition is by taking the analogy of a card game. The cards, the DNA sequence, have been dealt and will not change, however we need to understand how to play the cards, the rules, which is epigenetics. The guidelines can vary and completely change the way the card game is played and who comes out on top. The rules that are studied and understood through this research paper are those of DNA methylation and chromatin. These changes can produce
Methylation, specifically hypomethylation, can incessantly activate the transcription of oncogenic microRNAs which encourage carcinogenesis (Fukushige). Methylation, specifically hypermethylation, of the genome can turn off genes that can be transcripts to make microRNAs which actively work to suppress tumors. When a microRNA suffers from mutations, the altered miRNA can promote hypermethylation of tumor-suppressor genes (Lopez). DNA methylation affects the regulation of harmful, cancer-causing and can increase the incidence of pancreatic cancer. Cancer tissues were shown to have extraordinarily higher levels of methylation than non-cancerous tissues did
Epigenetic (defined as reversible regulation of various genome functions, occurring without change in DNA sequence)(6, 7) , modification has recently emerged as one of the
Epigenetics is the study of heritable modifications of your genes being expressed that are not manipulated by mutations in the DNA but by environmental factors. The increasing of inhibiting of transcribing genes is caused by epigenetic changes. The cells in the DNA are packaged together by proteins which are known as histones. DNA is wrapped around the protein (histones). Histone proteins and DNA are tagged chemically which alter gene expression. To impede DNA, DNA methylation is when a methyl group is added consisting of hydrogen and carbon molecules, which are used to limit gene expression. DNA methylation and Histone modification is most commonly known as an epigenetic modification. Epigenetic modifications are a long-term change in, which
Epigenetics tell your genes what to do. They are basically a switch turning a gene on or off. The research currently being done shows that the persons’ environment can directly affect their genes. Research being done by Michael Skinner shows that exposure to a known teratogen, pesticides, are having a direct impact on our genes. The pesticides are causing some epigenetics to turn on and others to shut off. This one example of how some teratogens are epigenetic influences. Yes, we need to be wary of where, when, how, and if we decide to use most household chemicals. There have been many studies showing that chemicals can affect our health. Further research needs to be done into epigenetics and teratogens in general and into household
Attending a Genetics and Biochemistry Masterclass first enabled me to appreciate the importance of mtDNA, and prompted me to read Lane’s “Power, Sex, Suicide”. Here I was introduced to the variety of hypotheses concerning the origin of the eukaryotic cell. The remaining uncertainty regarding the hydrogen hypotheses leaves such a vital step in our biological history a conundrum, making it an area I am interested in exploring further. The book also elucidated the importance of free-radical leakage in determining the rate of ageing, and the significance of deletions and single-base substitutions in causing this. My understanding of these genetic mutations was enhanced through “Life on the Edge” by
Human development from conception to adulthood is a conjoined partnership, moulded within our cells, of Nature (the DNA we inherit) and Nurture (the prevailing nutritional, social and physical environment). The field of epigenetic is quickly growing and with it the understanding that both the environment and individual lifestyle can also directly interact with the genome to influence epigenetic change. Developing organisms seem to have a wide range of susceptibility to epigenetic changes. Appropriate dynamics in epigenetic modifications are essential for embryogenesis, early fetal development and early postnatal growth. Consequently, the inadequate establishment of epigenetic modifications during critical developmental periods due to changes
Epigenetic changes may last throughout all cell divisions for the remainder of the cell’s life and for multiple generations (4).
Epigenetics can be hereditable or environmental factors that affect the expression of genes and lead to changes in gene expression. Unlike genetics, epigenetics does not only have to do with which genes are passed down to the offspring and the DNA sequence. The environmental conditions of the offspring’s parents impact the genes in their eggs and sperms by “switching on” certain genes and “switching of” others (Dowshen). Since the genes expression of the gametes are affect, the phenotypes of the offspring will change. Even in a person’s lifetime, environmental factors such as stress, chemical exposure, and diet can continue to impact gene expression through DNA methylation. During DNA methylation, a methyl group is randomly added to a 5-carbon cytosine ring, making 5-methylcytosine and these groups inhibit transcription. (Cheriyedath). Due the fact that transcription is not possible, the expressing of the genes in that section of the DNA strand will be suppressed. The attachment of the methyl group to DNA is not determined, which means that