Epigenetics: The Science of Change

Article:
Environ Health Perspect. 2006 Mar; 114(3): A160–A167.
doi: 10.1289/ehp.114-a160
PMCID: PMC1392256
PMID: 16507447
Environews
Focus
Epigenetics: The Science of Change
Bob Weinhold
Section 1- Vocabulary
Epigenetics- This is the study of the transformation of gene expression not caused by genetic alterations, but by change in factors such as environment and diet, causing variations in gene function.
Phenotype- the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment.
Environmental factors- An environmental factor, ecological factor or eco factor is any factor, abiotic or biotic, that influences living organisms.
Genetic difference- Genetic variation is a term used to describe the variation in the DNA sequence in each of our genomes. Genetic variation is what makes us all unique, whether in terms of hair color, skin color or even the shape of our faces.
Growth-  The development of an organism, e.g. of a plant from a seed to full maturity.
Genotype- The genotype is the part of the genetic makeup of a cell, and therefore of any individual, which determines one of its characteristics (phenotype).
DNA methylation- DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence.
Section 2 – Summary
Epigenetic modifications have long term-effects on gene expression. This can last up to more than one generation as observed in plants and animals.
Environmental elements affect gene expression and phenotypes. Factors trigger innate developmental potential in some species of both plants and animals. However, it may also have negative effects that can affect growth and development of disease.
Environmental factors including nutrition, chemical compounds, temperature variation, and other types of stressors influence phenotypical expression, and epigenetics in experimental model systems.
Recent studies with human samples have shown long-term effects of epigenetic alterations such as diet and exposure to chemical substances, and also other external experiences. The effects of epigenetics are particularly apparent when subjected to environmental factor happens during the gestation period.
A challenge in the research in this field particularly in humans, where it remains unclear to what extent epigenetic changes are involved. Parameters of environmentally induced phenotypes are hard to define.
3) The nursing application
Genetic variation among individual influence epigenetic deregulation. The environmental stresses are interpreted differently by each individual as a form of behavioral epigenetics.
DNA methylation and stable chromatic modifications mediate epigenetic phenomena in both plants and animals. Environmental factors have been identified as the element that establish epigenetic modification. Epigenetic expression can be found in both genetic and phenotypical expression. Exposure to chemicals, nutrition, temperature and other stressors has a significant impact on health. The underlying mechanisms remain largely unknown especially in human studies.
Epigenetics can be used to explain different biological phenomena. This knowledge can be used to describe the different aspects of human growth ad development and can be integrated to experience in birth, childhood, adulthood, menopause. The different external factors present in the chronological life affects the health and epigenetic expression. The human epigenome is subject to factors that can be traced from preconception to death where there are potential intervals where activity of epigenetics transpire. In nursing applications, epigenetics provide of a way of explaining how certain pathologies can be affected by epigenetic factors giving a more pro-active response to management of certain diseases. Epigenetic modification can influence the body in beneficial and permanent ways. Environmental elements can be altered to support healing and be used to improve personalized medicine.
INCLUDEPICTURE "/var/folders/_b/qsn5vkmj42g4gqcv85rqj6jm0000gn/T/com.microsoft.Word/WebArchiveCopyPasteTempFiles/logo-envhper.png" \* MERGEFORMATINET
Environ Health Perspect. 2006 Mar; 114(3): A160–A167. 
doi: 10.1289/ehp.114-a160
PMCID: PMC1392256
PMID: 16507447
Environews
Focus
Epigenetics: The Science of Change
Bob Weinhold
Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
For nearly a century after the term “epigenetics” first surfaced on the printed page, researchers, physicians, and others poked around in the dark crevices of the gene, trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence. Today, a wide variety of illnesses, behaviors, and other health indicators already have some level of evidence linking them with epigenetic mechanisms, including cancers of almost all types, cognitive dysfunction, and respiratory, cardiovascular, reproductive, autoimmune, and neurobehavioral illnesses. Known or suspected drivers behind epigenetic processes include many agents, including heavy metals, pesticides, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria, and basic nutrients.
In the past five years, and especially in the past year or two, several groundbreaking studies have focused fresh attention on epigenetics. Interest has been enhanced as it has become clear that understanding epigenetics and epigenomics—the genomewide distribution of epigenetic changes—will be essential in work related to many other topics requiring a thorough understanding of all aspects of genetics, such as stem cells, cloning, aging, synthetic biology, species conservation, evolution, and agriculture.
Go to:
Multiple Mechanisms
The word “epigenetic” literally means “in addition to changes in genetic sequence.” The term has evolved to include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells (although experiments show that some epigenetic changes can be reversed). There likely will continue to be debate over exactly what the term means and what it covers.
Many types of epigenetic processes have been identified—they include methylation, acetylation, phosphorylation, ubiquitylation, and sumolyation. Other epigenetic mechanisms and considerations are likely to surface as work proceeds. Epigenetic processes are natural and essential to many organism functions, but if they occur improperly, there can be major adverse health and behavioral effects.
Perhaps the best known epigenetic process, in part because it has been easiest to study with existing technology, is DNA methylation. This is the addition or removal of a methyl group (CH3), predominantly where cytosine bases occur consecutively. DNA methylation was first confirmed to occur in human cancer in 1983, and has since been observed in many other illnesses and health conditions.
Another significant epigenetic process is chromatin modification. Chromatin is the complex of proteins (histones) and DNA that is tightly bundled to fit into the nucleus. The complex can be modified by substances such as acetyl groups (the process called acetylation), enzymes, and some forms of RNA such as microRNAs and small interfering RNAs. This modification alters chromatin structure to influence gene expression. In general, tightly folded chromatin tends to be shut down, or not expressed, while more open chromatin is functional, or expressed.
One effect of such processes is imprinting. In genetics, imprinting describes the condition where one of the two alleles of a typical gene pair is silenced by an epigenetic process such as methylation or acetylation. This becomes a problem if the expressed allele is damaged or contains a variant that increases the organism’s vulnerability to microbes, toxic agents, or other harmful substances. Imprinting was first identified in 1910 in corn, and first confirmed in mammals in 1991.
Researchers have identified about 80 human genes that can be imprinted, although that number is subject to debate since the strength of the evidence varies. That approximate number isn’t likely to rise much in years to come, writes a team including Ian Morison, a senior research fellow in the Cancer Genetics Laboratory at New Zealand’s University of Otago, in the August 2005 Trends in Genetics. Others in the field disagree. Randy Jirtle, a professor of radiation oncology at Duke University Medical Center, and his colleagues estimated in the June 2005 issue of Genome Research that there could be about 600 imprinted genes in mice; in an October 2005 interview Jirtle said he’s anticipating a similar tally for humans, even though the known imprintable genes of mice and people have an overlap of only about 35%.
Go to:
Links to Disease
Among all the epigenetics research conducted so far, the most extensively studied disease is cancer, and the evidence linking epigenetic processes with cancer is becoming “extremely compelling,” says Peter Jones, director of the University of Southern California’s Norris Comprehensive Cancer Center. Halfway around the world, Toshikazu Ushijima is of the same mind. The chief of the Carcinogenesis Division of Japan’s National Cancer Center Research Institute says epigenetic mechanisms are one of the five most important considerations in the cancer field, and they account for one-third to one-half of known genetic alterations.
Many other health issues have drawn attention. Epigenetic immune system effects occur, and can be reversed, according to research published in the November–December 2005 issue of the Journal of Proteome Research by Nilamadhab Mishra, an assistant professor of rheumatology at the Wake Forest University School of Medicine, and his colleagues. The team says it’s the first to establish a specific link between aberrant histone modification and mechanisms underlying lupus-like symptoms in mice, and they confirmed that a drug in the research stage, trichostatin A, could reverse the modifications. The drug appears to reset the aberrant histone modification by correcting hypoacetylation at two histone sites.
Lupus has also been a focus of Bruce Richardson, chief of the Rheumatology Section at the Ann Arbor Veterans Affairs Medical Center and a professor at the University of Michigan Medical School. In studies published in the May–August 2004 issue of International Reviews of Immunology and the October 2003 issue of Clinical Immunology, he noted that pharmaceuticals such as the heart drug pro-cainamide and the antihypertensive agent hydralazine cause lupus in some people, and demonstrated that lupus-like disease in mice exposed to these drugs is linked with DNA methylation alterations and interruption of signaling pathways similar to those in people.
Go to:
Substantial Changes
Most epigenetic modification, by whatever mechanism, is believed to be erased with each new generation, during gameto-genesis and after fertilization. However, one of the more startling reports published in 2005 challenges this belief and suggests that epigenetic changes may endure in at least four subsequent generations of organisms.
Michael Skinner, a professor of molecular biosciences and director of the Center for Reproductive Biology at Washington State University, and his team described in the 3 June 2005 issue of Science how they briefly exposed pregnant rats to individual relatively high levels of the insecticide methoxychlor and the fungicide vinclozolin, and documented effects such as decreased sperm production and increased male infertility in the male pups. Digging for more information, they found altered DNA methylation of two genes. As they continued the experiment, they discovered the adverse effects lasted in about 90% of the males in all four subsequent generations they followed, with no additional pesticide exposures.
The findings are not known to have been reproduced. If they are reproducible, however, it could “provide a new paradigm for disease etiology and basic mechanisms in toxicology and evolution not previously appreciated,” says Skinner. He and his colleagues are conducting follow-up studies, assessing many other genes and looking at other effects such as breast and skin tumors, kidney degeneration, and blood defects.
Other studies have found that epigenetic effects occur not just in the womb, but over the full course of a human life span. Manel Esteller, director of the Cancer Epigenetics Laboratory at the Spanish National Cancer Center in Madrid, and his colleagues evaluated 40 pairs of identical twins, ranging in age from 3 to 74, and found a striking trend, described in the 26 July 2005 issue of Proceedings of the National Academy of Sciences. Younger twin pairs and those who shared similar lifestyles and spent more years together had very similar DNA methylation and histone acetylation patterns. But older twins, especially those who had different lifestyles and had spent fewer years of their lives together, had much different patterns in many different tissues, such as lymphocytes, epithelial mouth cells, intra-abdominal fat, and selected muscles.
As one example, the researchers found four times as many differentially expressed genes between a pair of 50-year-old twins compared to 3-year-old twins, and the 50-year-old twin with more DNA hypomethylation and histone hyperacetylation (the epigenetic changes usually associated with transcriptional activity) had the higher number of overexpressed genes. The degree of epigenetic change therefore was directly linked with the degree of change in genetic function.
Sometimes the effects of epigenetic mechanisms show up in living color. Changes in the pigmentation of mouse pup fur, ranging from yellow to brown, were directly tied to supplementation of the pregnant mother’s diet with vitamin B12, folic acid, choline, and betaine, according to studies by Jirtle and Robert Waterland published in August 2003 (issue 15) in Molecular and Cellular Biology. The c...