Full Answer
What is the role of DNA methylation in common human diseases?
In addition to genomic imprinting and cancer, the important role of DNA methylation in common human diseases has recently been revealed. In the subsequent sections, we discuss some recent findings on DNA methylation in these common human diseases using autoimmune diseases, metabolic disorders, psychological disorders, and aging as examples.
What is aberrant DNA methylation in cancer?
Aberrant DNA methylation of imprinted loci has been widely observed in many cancer types, such as colon, breast, liver, bladder, Wilms, ovarian, esophageal, prostate, and bone cancers.
Can DNA methylation predict cancer outcomes?
DNA Methylation as a Therapeutic Target Epigenetic aberrations in cancers including differential DNA methylation can be used to distinguish tumor subtypes, indicate treatment responsiveness, predict clinical outcomes, and detennine therapeutic strategies.
What type of reaction is DNA methylation?
Mammalian DNA methylation primarily occurs as a covalent addition of methyl group to the carbon-5 atom of cytosine in a cytosine-guanine (CpG) dinucleotide. This enzymatic reaction is catalyzed by three DNA methyltransferases (DNMTs).
What diseases are caused by DNA methylation?
DNA methylation, a process of adding a methyl group to DNA done by a DNA methyltransferase is a heritable (epigenetic) alteration leading to cancer, atherosclerosis, nervous disorders (Imprinting disorders), and cardiovascular diseases.
What diseases can be treated with epigenetics?
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.
What kinds of disorders in humans are associated with improper methylation?
89, 90 Interestingly, in contrast with normal people, accelerated DNA methylation age is found in individuals with diseases such as PD,91 Huntington's disease,92 and Alzheimer's disease,93 as well as some viral infections.
What is DNA methylation used for?
DNA methylation is essential for silencing retroviral elements, regulating tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. Importantly, DNA methylation in different genomic regions may exert different influences on gene activities based on the underlying genetic sequence.
How is Angelman syndrome an example of epigenetics?
One of the epigenetic research models in Angelman syndrome (AS). This neurologic disorder associated with improper central nervous system development and function, together with Prader-Willi syndrome are caused by the defects of epigenetic regulation.
What is an epigenetic disease?
Disease may be caused by direct changes in epigenetic marks, such as DNA methylation, commonly found to affect imprinted gene regulation. Also described are disease-causing genetic mutations in epigenetic modifiers that either affect chromatin in trans or have a cis effect in altering chromatin configuration.
What is Angelman syndrome caused by?
Angelman syndrome is a genetic disorder. It's usually caused by problems with a gene located on chromosome 15 called the ubiquitin protein ligase E3A (UBE3A) gene.
How is Angelman syndrome diagnosed?
A definitive diagnosis can almost always be made through a blood test. This genetic testing can identify abnormalities in your child's chromosomes that indicate Angelman syndrome. A combination of genetic tests can reveal the chromosome defects related to Angelman syndrome.
What does Angelman syndrome look like?
In some cases, individuals with Angelman syndrome may have distinctive facial features including a prominent chin, deep-set eyes, an abnormally wide mouth (marcostomia) with a protruding tongue, widely-spaced teeth and an abnormally flat back of the head (brachycephaly).
Does Lupus change your DNA?
Lupus has also been shown to be associated with reduced expression of DNA cytosine-5-methyltransferases, which have hypomethylation activity that might be responsible for the production of autoreactive antibodies.
How do you determine DNA methylation?
Currently, there are three primary methods to identify and quantify DNA methylation. These are: sodium bisulfite conversion and sequencing, differential enzymatic cleavage of DNA, and affinity capture of methylated DNA (1). Restriction enzyme based differential cleavage of methylated DNA is locus-specific.
Why is methylation important in the body?
The methylation cycle helps us to operate both physically and mentally, so it may not be surprising that many different functions in the body use this process. Such functions include nervous, cardiovascular and immune system activity,5-8 as well as energy production, heavy-metal detoxification and hormone balance.
Role of DNA methylation in Disease
DNA methylation plays key roles in gene expression and regulation. It is an epigenetic signaling tool that locks genes in the “off position” and is an important component in various cellular processes such as genomic imprinting, embryonic development, maintenance of chromosome stability, and X-chromosome inactivation.
Regulation of DNA methylation by methyltransferases
DNA methylation involves the addition of a methyl group to the 5-carbon of the cytosine ring, which results in 5-methylcytosine or 5-mC. These methyl groups inhibit transcription by occupying the DNA’s major groove. 5-mC constitutes about 1.5% of genomic DNA.
Significance of DNA methylation
The role of DNA methylation in gene expression varies across different kingdoms of organisms. 5’—C—phosphate—G—3′ (CpG) methylation is distributed fairly globally in mammals, whereas among invertebrates, the methylation pattern is generally “mosaic,” with heavily methylated DNA regions being interspersed with regions that are not methylated.
DNA methylation and disease
Since DNA methylation plays such an important role in gene expression, it seems obvious that faulty methylation could have devastating consequences, including human disease.
Methylation analysis using EpiTYPER chemistry from Agena Bioscience
The DNA methylation analysis technology, EpiTYPER MassARRAY, provided by Agena Bioscience Agena Bioscience (previously Sequenom Inc.), is one of the most reliable quantitative methods available today for DNA methylation analysis.
The role of DNA methylation in normal biologic processes
The role and position of DNA methylation varies among different kingdoms of organisms. As mentioned above, mammals tend to possess a fairly global distribution of CpG methylation, while invertebrate animals typically show a "mosaic" pattern of methylation.
DNA methylation and disease
Scientists first discovered the role of DNA methylation in human diseases while studying genomic imprinting. Genomic imprinting is a stable and heritable phenomenon that occurs independently from classical Mendelian processes.
Technologies used to investigate DNA methylation
According to Pfeifer, “Most of the conventional methods for the analysis of DNA methylation patterns are based on converting cytosine to uracil by chemical deamination using high temperature and high concentrations of sodium bisulfite, while some newer methods use enzymes for deamination.” Typically, pathologists face difficulties in predicting biomarkers for cancer and representing the overall status of tumor mass from small biopsy tissue samples or liquid samples obtained from patients with lung cancer.
Methodological challenges in DNA methylation studies
Many methods are used to study DNA methylation, and each has its own limitations. For instance, as stated above, the chemical treatment associated with the bisulfite-based method causes DNA degradation and shorter DNA fragments are obtained for further analysis.
DNA methylation and clinical benefits
Abnormal DNA methylation is associated with many diseases and DNA methylation-based biomarkers can help to improve disease prognosis and treatment response. “One area of clinical interest in the DNA methylation field is to exploit altered DNA methylation patterns for cancer diagnosis.
What is the role of DNA methylation in human diseases?
The role of DNA methylation in human diseases was first explored in the context of genomic im printing . Genetic imprinting is an epigenetic phenomenon in which the maternal and paternal alleles are expressed in a parent-of-origin-specific manner. Genomic imprinting is stable and heritable during mitosis.11 A relatively well-studied imprinting locus in humans is the insulin-like growth factor 2 (IGF2)/H19 region, located on chromosome 11p15.5, in which DNA methylation on the imprinting control region (ICR) regulates the binding of zinc-finger CCCTC-binding factor (CTCF) and subsequent gene expression.12 Loss of imprinting (LOI) causes many disorders such as Beckwith–Wiedemann Syndrome and cancer (which will be discussed later). Similarly, LOI of paternally-inherited chromosome 15q11.2-q13 is observed in Prader–Willi syndrome,13 and LOI of this region is also implicated in Angelman syndrome. 14
Why is DNA methylation important?
With the abundance of emerging evidence indicating the important role of DNA methylation in common diseases, researchers have attempted to use DNA methylation as a biomarker to identify epigenetic changes that are associated with disease status.
What is DNA methylation?
DNA methylation is one of the earliest epigenetic modifications found in humans.5 It is a type of post-replication modification that often occurs in cytosines of the CpG dinucleotide sequence with the help of DNA methyltransferases (DNMTs),6 which transfer a methyl group from S-adenyl methionine to the fifth carbon of a cytosine residue to form 5-methylcytosine (5mC). The process of demethylation is more complex and can be passive or active. Ten-eleven translocation (TET) enzymes oxidize 5mCs 7, 8 and promote locus-specific removal of DNA methylation. 9 Specifically, in the presence of water, oxygen, and α-ketoglutarate, 5mC becomes 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) through stepwise oxidation, yielding carbon dioxide and succinate.9 Then both 5fC and 5caC can be replaced by an unmodified cytosine through thymine DNA glycosylase-mediated base-excision repair. 8, 10
What is epigenetics in biology?
The term “epigenetics” was coined by Conrad Hal Waddington, a British developmental biologist in 1942, to describe the “whole complex of developmental processes” linking genotype and phenotype. 1, 2 Since then, this concept has changed several times, 3, 4 and recent studies on epigenetics at the molecular level mainly cover changes in DNA methylation, histone modifications, non-coding RNAs, and higher-order chromatin structure. Even though the role of epigenetics was first recognized in development, an increasing amount of evidence has shown that it is also related to the development and progression of many common diseases. Here, we first review the role of epigenetics, and mainly DNA methylation, in common human diseases.
Is DNA methylation a modifier?
However, in the development of common diseases, DNA methylation can be a mediator, modifier, or even consequence of the disease.
Is epigenetics related to development?
Even though the role of epigenetics was first recognized in development, an increasing amount of evidence has shown that it is also related to the development and progression of many common diseases . Here, we first review the role of epigenetics, and mainly DNA methylation, in common human diseases.
Is DNA methylation a metabolic disorder?
DNA methylation in metabolic disorders. Hyperglycemia (which can lead to type I and type II diabetes), hyperlipidemia (such as obesity-related conditions), and many diseases associated with these two phenomena, such as cardiovascular diseases, are currently a huge risk of death.
What is the role of methylation in the body?
This is an important job. Methylation is the process by which methyl molecules are added to enzymes, hormones, and neurotransmitters as well as to DNA itself. This can impact physiological and psychiatric issues such as mood, memory, concentration, and sleep.
What is methylation disorder?
Methylation Disorders: Overmethylation and Undermethylation. Methylation disorders are often closely associated with mental illness. When the methylation system is properly balanced the symptoms of mental illness will wane. Genetic mutations can cause abnormalities in the body’s methylation cycle. The methylation cycle is a series ...
What happens when the methylation system is balanced?
When the methylation system is properly balanced the symptoms of mental illness will wane. Genetic mutations can cause abnormalities in the body’s methylation cycle. The methylation cycle is a series of biochemical pathways, interdependent, and often easily misunderstood.
What is an overmethylated person?
Most overmethylated persons are very passionate individuals and often self sacrificing. These individuals may be attracted to professions or hobbies in music and the arts, theater, acting, social services or causes, and philosophy. They often march to the beat of their own drum.
What is undermethylated in the general population?
Many undermethylated persons in the general population tend to be high-achievers and have good mental health. These people tend to be our doctors, lawyers, educators, secretaries, corporate executives, professional athletes and scientists who strive for high career accomplishment.
Where is the methylation cycle found?
The methylation cycle is found in all the cells of the body except for our red blood cells. It regulates many substances that are necessary for the body to function. For the methylation cycle to work properly, our bodies need an appropriate balance of certain nutrients.
Can you be undermethylated on Zoloft?
You may be undermethylated if you are a perfectionist and highly competitive.
Regulation of DNA Methylation by Methyltransferases
Significance of DNA Methylation
- The role of DNA methylation in gene expression varies across different kingdoms of organisms. 5’—C—phosphate—G—3′ (CpG) methylation is distributed fairly globally in mammals, whereas among invertebrates, the methylation pattern is generally “mosaic,” with heavily methylated DNA regions being interspersed with regions that are not methylated. The significance of 5-mC as a k…
DNA Methylation and Disease
- Since DNA methylation plays such an important role in gene expression, it seems obvious that faulty methylation could have devastating consequences, including human disease. Researchers have conducted many studies examining the association between errors in this methylation and diseases such as cancer, muscular dystrophy, lupus, and various birth d...
Methylation Analysis Using EpiTYPER Chemistry from Agena Bioscience
- The DNA methylation analysis technology, EpiTYPER MassARRAY, provided by Agena Bioscience Agena Bioscience (previously Sequenom Inc.), is one of the most reliable quantitative methods available today for DNA methylation analysis. EpiTYPER is a MALDI-TOF mass spectrometry-based bisulfate sequencing method that enables region-specific DNA methylation …