BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: DNA Methylation

The journey to find a cure for cancer

What exactly does ‘epigenetic’ mean? Well epigenetic literally means “in addition to changes in genetic sequence.” The term now means any procedure to change genetic activity without changing the sequence of the actual DNA. So why is this important? Epigenetics can affect a lot of scientific research. For example DNA methylation is a hugely important epigenetic modification.

DNA methylation is where a methyl group would be added to a cytosine in a DNA sequence changing its function. This can be used in embryonic development, X-chromosome inactivation, genomic imprinting, gene suppression, carcinogenesis and chromosome stability. This means DNA methylation is very vital to growth and development- as it is a natural process- however can affect bad cells.

Examples of this are with cancer cells. DNA Methylation patterns- adding a group- are interrupted and changed when cancer is present. DNA methylation done on the promoters in tumor cells can turn off the expression of genes. In humans this can cause disruption of vital developmental pathways. This was then tested in an experiment (for now we will only observe human results because it was tested on mice as well) They tested human normal brain tissue vs. cancerous.

After testing the DNA methylation patterns on tumors, they found that 121 loci (loci is the central “hot spot” of genes) had strong methylation compared to the normal brain tissue which had 60% less. So what does all this mean??

Basically DNA methylation is a good thing in a normal environment. When cancer is present DNA methylation can change and be harmful in a negative environment such as a tumor because it causes hypermethylation.

While the take away is essentially the obvious- cancer is bad- scientists can use this data to find a correct cure for cancer and to create better medicine as some can harm even more by increasing DNA methylation in tumors. For more information on this click here.

 

 

 

DYING to Know Your Predicted Lifespan? Look No Further!

Have you ever wondered how long you’ll be around for? Well, scientists at the German Cancer Research Center, Saarland Cancer Registry, and the Helmholtz Research Center for Environmental Health have made great strides in predicting human mortality. How so? Through a controlled study in which they analyzed patterns in DNA methylation.

DNA methylation, an epigenetic phenomenon, occurs in the body in order to inhibit the transcription of DNA. Methyl groups attach to specific combinations of DNA building blocks called CpGs. In this experiment, the scientists analyzed the DNA from blood cells taken from 1,900 participants fourteen years prior. As they were all older adults, many of the participants had died within that fourteen years. The scientists analyzed methylation at 500,000 of the CpGs, trying to figure out if there was a correlation to chances of survival. Spoiler alert: at 58 of these CpGs there proved to be a strong correlation between methylation level and mortality.

One interesting discovery was that 22 out of the 58 influential CpGs were identical (in terms of amount of methylation) to the CpGs of smokers that the scientists had analyzed in a previous study. What does this mean? Smoking definitely leaves its mark on your genome. However, the good news is that DNA methylation can be reversed, so if a smoker quits his or her risk of dying could drop significantly.

The second major finding of this study was that only 10 out of the 58 CpGs can actually determine mortality risk. The scientists took the 10 CpGs with the strongest correlation with mortality and created an epigenetic risk profile. This profile can predict “all-cause mortality”. Participants who were overly-methylated at five or more of these spots were seven times more likely to die in the fourteen year span than their properly-methylated counterparts.

This study is a major breakthrough in understanding human mortality, because analyzing DNA methylation is so much more accurate than looking at SNPs. The researchers plan on using their new knowledge to find out how to improve methylation profiles at these CpGs.

Does it surprise you that only 10 spots on the genome can have such a profound effect on duration of life? Do you think there could be an even more accurate predictor of mortality than DNA methylation levels? Let me know in the comments!

Don't Smoke!

Credit: Nina Matthews Photography, URL: https://www.flickr.com/photos/21560098@N06/5642711277

Original Article: https://www.sciencedaily.com/releases/2017/03/170320104008.htm

How A Chemical From the Cypress Tree Could Advance Epigenetics Against Cancer

by Czechmate on Wikimedia Commons

Found in the essential oil extracted from the bark of a cypress tree, a chemical named hinokitiol shows potential to impact epigenetic tags on DNA and stop the activity of genes that assist the growth of tumors.

In order to develop an of understanding cancer, researches have had to comprehend the DNA methylation, an epigenetic function which controls gene expression. In regular DNA methylation, genes that work to fight against tumors are turned on, reducing the risk of cancer. However, if DNA methylation is negatively altered, then those cancer-fighting genes will be silenced, helping to progress cancer development. Scientists have tried to combat irregular DNA methylation and over-silencing of genes by creating epigenetic anti-cancer medications that reverse non-beneficial methylation effects. Like in most cases of medication usage, the users face unappealing side effects. Hinokitiol is attractive to scientists because it is a natural compound with many health benefits and way less side effects than modified drugs that can possibly cause mutagenesis and cytotoxicity.

 

Researchers from the Korea University College of Medicine tested the productivity of the hinokitiol chemical in a study by giving doses of it to colon cancer cells. It was found that this chemical helped to inhibit the colon cancer cells efficiency without affecting the colon cells without cancer. The scientists also found through careful inspection that the presence of hinokitiol decreases the expression of proteins DNMT1 and UHRF1; both of which are proteins that encourage carcinogenesis. In summary, the doses of hinokitiol appear to have allowed normal cells to remain healthy, while reducing the ability for the colon cancer cells to thrive and ceasing the production of proteins that promote cancer maturation.

Researchers are continuing their search for natural compounds, as opposed to artificial medications, that can prevent the flourishing of cancer in our bodies through playing a positive role in gene expression and DNA methylation.

http://www.whatisepigenetics.com/cypress-trees-epigenetically-protect-cancer/

 

 

https://commons.wikimedia.org/wiki/File:Raindrops_on_leyland_cypress.jpg

Long Term Effects of Bad Diet Linked to Epigenome

Epigenetics has become an increasingly popular topic of scientific study. It is universally understood that DNA carries genes, however the expression of those genes are at the whim of the epigenome. The long-term control of the epigenome over the expression of certain genes is not yet fully understood. Scientist Erik van Kampen of the Leiden Academic Centre for Drug Research at Leiden University in The Netherlands studies epigenetics. He was interested in the mystery of how the epigenome is influenced by diet. He explored the idea of how the effects of a poor diet continue to persist even after a better diet is adopted.

In his study, he used mice that naturally had a high susceptibility to getting high blood cholesterol and atherosclerosis. He fed these mice either a high fat, high-cholesterol diet or a normal diet. After time had passed, bone marrow was isolated from both the unhealthy and healthy diet mice. This bone marrow was transplanted into mice that had their bone marrow destroyed. The new mice with borrowed bone marrow were given a healthy, normal diet for several months. After this time had passed, the mice were measured for development of atherosclerosis in the heart. In addition to this, the mice were measured for the number and status of immune cells throughout the body and epigenetic markings on the DNA in the bone marrow.

The results of this study were staggering. Mr. Kampen found that DNA methylation (which inactivates the expression of genes) in the bone marrow was different in both types of mice. The transplants received from the unhealthy diet mice were seen as having a decreased immune system and increased atherosclerosis in comparison to the ones who had healthy donors. This study proves at least somewhat of a correlation between diet and long-term effects on the body and the expression of genes.

The original article can be found at this address: http://www.sciencedaily.com/releases/2014/11/141103102359.htm

Does the aging process influence changes on a cellular level or do changes on a cellular level influence the aging process?

wrinkles

How do humans age? While we are “programmed to die,” there doesn’t seem to be one thing that causes our death by “old age.” For example, one way we carry out our own deaths is found on the cellular level, where we accumulate mutations in the DNA repair process and the cells themselves die, or the enter senescence (non-replicating state) as they age. These processes occur at several different times, overlapping and alternating. Therefore, what appears to be the best time to intervene in order to promote healthy aging? No one knows, but they do know what DNA becomes extremely damaged as time goes on and has an incredible impact on our aging process. The cells have sooner suicide dates where they undergo apoptosis more rapidly than normal, and the loss of too many cells can cause tissue atrophy and dysfunction. In addition to creating a lack of cells, the damaged DNA can even shift epigenetic markers.

Typically, epigenetic marks shift in tumor cells, which can lead to cancerous cells. However, in the early 1990s at Johns Hopkins University, Jean-Pierre Issa was studying changes in DNA methylation in colon cancer cells when he observed shifts in epigenetic markers over time, but not only in tumor cells; he found that (to a lesser degree) these shifts were occurring in healthy cells as well. After mapping DNA methylation in human cells, we know that some areas of the genome become hypermethylated with age while others exhibit reduced methylation. These changes typically occur through DNA replication or DNA damage repair because the histone modifications are not always perfectly reproduced and in order to repair damaged DNA, repair proteins must remove the epigenetic marks to access the damaged genetic material to repair it, and once completed, the epigenetic marks can be omitted or misplaced. These epigenetic alterations have been linked to a reduced regenerative capacity of stem cells with age, and bring up a valuable question:

“Is this an epiphenomenon that happens just because we age, or is it actually causing symptoms or diseases of aging and limiting life span?”

Article source: http://www.the-scientist.com/?articles.view/articleNo/42280/title/How-We-Age/

Fear in Your Genes

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Scientists at the University of Virginia recently conducted a study that suggests a connection between social behaviors and epigenetic markers. The study of these markers could predict the social dispositions of individuals and predict future social issues.

The gene for Oxytocin receptor (OXTR) has the ability to carry various amounts of DNA methylation tags. Those low in methyl tags have a greater ability to utilize oxytocin and therefore have a less amplified fear response. Those with many DNA methyl tags are shown to exhibit a more exaggerated fear response. More finitely, the amount of OXTR methylation affected the amount of brain activity in the amygdala, fusiform, and insula. These regions of the brain are directly correlated with face and emotional processing. To prove this, researchers conducted MRI scans on healthy participants while showing them pictures of angry and fearful faces.

The study not only proved the importance of studying the possible effects of epigenetic markers on susceptibility and resistance to disease, but it also shed a light on the possibility of brain disorders such as autism, anorexia, and depression being linked to DNA methyl tags at the oxytocin receptor.

Broadly, this study changes the way we look at how our environment and upbringing shapes our future susceptibility to illness and disorders. As scientific investigation into this topic continues and expands, we may be able to predict an individual’s reaction to social situations with the prick of a finger.

Article Source: http://www.genengnews.com/gen-news-highlights/fear-response-may-be-epigenetically-amplified-or-muted/81250914/

Regular Exercise Can Change Our DNA

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Most people (hopefully) know that exercise and physical activity are beneficial to almost everyones physical and mental health. Exercising improves one’s mood, boosts energy, controls weight, helps the body fight against diseases, reduces stress, and many more life benefits. A new study  by a group of scientists in Sweden discovered how the influence of physical exercise actually has that beneficial effect on the human body.

The scientists focused their work on 23 young, healthy men and women at the Karolinska Institute in Stockholm. The participants were asked to exercise on stationary bikes for 45 minutes, four times per week, for three months. The scientists understood that it would be difficult to study the full changes on each person because they can’t isolate the other aspects of someone’s life like diet or other behaviors. Because of this issue, each person only exercised one leg so they essentially became their own control group.

After the three months had passed, the scientists clearly saw that the exercised leg was stronger. They also studied the DNA of the muscle cells and compared them between each leg. The genome of muscle cells on the exercised leg had new methylation patterns. DNA Methylation is the process of methyl groups attaching to the outside of a gene and making the gene more or less able to respond to biochemical signals. This entire study is also known as epigenetis. Epigenetics is the study of modifications of DNA influenced by the environment. The scientists found that exercise has a huge effect on human epigenetics based on methylation patterns.

The experiment showed that many of the methylation changes were on the enhancer part of the genome. Enhancers “bind to activator proteins which help connect transcription factors to RNA polymerase and the promotor region to turn on transcription of a gene” (from Mrs. Newitt notes packet). The enhancers amplified the expression of proteins by genes that effect energy, insulin, muscle inflammation and muscle pain.

Exercising is good for you and now we know why. It affects how healthy and fit our muscles become. The results of this study will now help lead other scientists into methylation pattern and gene expression research.

 

Main article:

http://well.blogs.nytimes.com/2014/12/17/how-exercise-changes-our-dna/?_r=0

Other articles of interest:

http://www.ncbi.nlm.nih.gov/pubmed/25484259

http://learningenglish.voanews.com/content/study-regular-exercise-can-change-our-dna/2580467.html

http://www.cell.com/cell-metabolism/abstract/S1550-4131(12)00005-8?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413112000058%3Fshowall%3Dtrue

http://www.mayoclinic.org/healthy-living/fitness/in-depth/exercise/art-20048389?pg=1

Can Stress Affect Pregnancies in Later Generations?

We all know stress isn’t always a good thing, but it could be important to especially avoid it at certain points in one’s life. Recently researchers from the University of Lethbridge in Canada investigated the effects of stress on pregnancies and how it can influence pre-term births. It is already known that pre-term births them selves lead to health issues later in life, but there were some new discoveries involving epigenetics.

 

Epigenetic_mechanisms

 

These researchers studied the length pregnancies of rats, due to the generally small amounts of variation between them, and found something intriguing. They carried out the experiment by first splitting the first generation of rats into “stressed” and “not stressed” groups. What they found was that the daughters of stressed rats had a shorter pregnancy than the daughters of not stressed rats.

This trend continued into the granddaughters of the rats. They also displayed high levels of glucose than the control group, and they weighed less. The stress also compounded, or increased, through generations.

This can all translate into human pregnancies. The researchers believe that the epigenetic changes in the rats is due to microRNA (miRNA) – non-coding RNA molecules that play a role in regulating gene expression. They bind to complementary mRNAs and prevent them from being translated. This is different than what is usual belief with epigenetics which is that epigenomes are affected by DNA methylation of the nucleotide base pairs. Metz, a scientist working on this research states that microRNAs “are important biomarkers of human disease, can be generated by experiences and inherited across generations. We have now shown that maternal stress can generate miRNA modifications with effects across several generations.”

It is very similar to the information found with the generational epigenetic effects of famine in the “Ghost in Our Genes” video that we watched in class.

This research can help determine pre-term births and the causalities that can come along with them. While the research is still not the whole picture, it is another step towards understanding our genetics.

 

Diesel Exhaust Causes Changes Within

Diesel Exhaust

Two hours of exposure to diesel exhaust fumes has proven to show fundamental health-related changes in biology by switching some genes on and others off.

A study put volunteers in a polycarbonate-enclosed booth and had them breath diluted and aged exhaust fumes. These fumes were about equal to the air quality along a Beijing highway. The researchers examined how the exposure affected the chemical coating that attaches to many parts of a person’s DNA. The coating they were referring to is carbon-hydrogen coating, also known as methylation. The coating can silence or dampen a gene and prevent it from producing a protein. Methylation is a mechanism for controlling gene expression.

The study found that diesel exhaust caused changes in methylation located at about 2,800 different places along a person’s DNA, which affects about 400 genes. Some places led to more methylation. How these changes affect health is the next topic of research. However, the AstraZeneca Chair in Occupational and Environmental Lung Disease claims that the fact that DNA methylation was affected from only two hours of exposure is a positive implication; when something happens that quickly, it usually means you can reverse it through either therapy, change in environment, or change in diet.

This article is very similar to what we are learning about methylation and epigenetics. It discusses how the environment can affect someone’s genes and their gene expression as opposed to solely being their DNA sequence. I found this interesting because diesel exhaust is something people are exposed to everyday and it is important to know the affects it can have other than just respiratory issues.

Source:

http://www.eurekalert.org/pub_releases/2015-01/uobc-bid010715.php

http://aqicn.org/city/beijing/

http://www.whatisepigenetics.com/dna-methylation/

http://commons.wikimedia.org/wiki/File:Diesel-smoke.jpg

Identical but Not the Same

 

Some Rights Reserved. More Information: http://www.flickr.com/photos/timoni/3390886772/sizes/s/in/photostream/

After studying genetically inherited traits and diseases it could be easy to assume that genes determine everything about us. While it is true that colorblindness is a sex-linked trait – there is certainly more to the story.

Monozygotic “identical” twins are genetically identical, so they should be the same in all ways shouldn’t they?

Why, then, does one twin get early onset Alzheimer’s disease and the other “identical” twin doesn’t? The same is true for height, autism, and cancer. Although, when one twin has a disorder the other is more likely to get the disease also, that is not always the case.

In the January edition of National Geographic, author Peter Miller discusses the newest theories about how genes, environoment and epigenetics affect our life (and the end of it).

Twins offer scientists a unique opportunity to study how genetically identical people differ. Basically, that means scientists can study how things other than genes affect human development and lifespan. Already, scientists have found that a persons height is only 80% determined by genetics because the heights of “identical” twins differ by about .o8 on average. Using IQ tests, scientists have nearly disproved John Locke’s Tabula Rasa or blank slate theory (the idea that children are born with a blank mind that is either stimulated – (and made intelligent) – or not –  (kept unintelligent)). Specifically, scientists studied twins who had been separated at birth and adopted into different families. In this way, scientists have found that intelligence  is about 75% controlled by genetics.

So that leads to the question, what is it besides genes that affects us humans so drastically?

Environment has something to do with our differences. However, that cannot be the whole story. “The Jim Twins” as they are called in the twin science community, were studied in the 1870’s. They were adopted into different families where both boys were named Jim. Then went on to have the same jobs, marry wives of the same name (two Lynda’s first then two Betty’s), enjoy the same hobbies, enjoy the same brand of cigarette and beer, name their sons James Allan and James Alan… the list goes on. These two lived very similar lives, yet they grew up in very different environments. If environment isn’t the only factor in creating difference then what is?

Scientists have recently come to believe that epigenetics plays a significant role in our lives. Epigenetics (site 2) can be seen as the meshing of environment and DNA. In the words of author Peter Miller “If you think of our DNA as an immense piano keyboard and our genes as keys – each key seach key symbolizing a segment of DNA respinsible  for a particulare note or trait, and all the keys combining to make us who we are – then epigenetic prcesses determine when an how each key can be struck changing the tune.”  Environmental changes do have some impact.  When a pregnant mouse is put under stress during the pregnancy it can create changes in the fetus that lead to abnormal behavior as the rodent grows into adulthood.

However, scarily enough, many epigenetic changes appear to occur randomly (thus creating a probelm for the organized nature/nurture theory). Currently work is being done studying DNA methylation, which is known to make the expression of genes weaker or stronger. Specifically, Andrew Feinburg, director of the Center for Epigenetics at Johns Hopkins School of Medicine, is working to find how DNA methylation relates to autism. Currently, he is using scanners and computers to search samples of DNA from autistic twins who have the disease in varying degrees. He is looking to compare how and why

the genes are expressed differently.

In the end, all we know is that there is more to our future than our genes can tell us. Yes, our genes play a huge role in who we are as people – in terms of appearance, character, intelligence and more – but there are some variables that our environment and epigenetics control.

Main Article: Miller, Peter. “A Thing or Two About Twins.” National Geographic. Jan 2012: 38-65. Print.

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