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Epigenetics and the Human Brain

Throughout our lives, the brain remains flexible and responsive. In addition to receiving signals from the outside world, the brain allows us to form memories and learn from our experiences. Many brain functions are accompanied at the cellular level by changes in gene expression. Epigenetic mechanisms such as histone modification and DNA methylation stabilize gene expression, which is important for long-term storage of information.

Not surprisingly, epigenetic changes are also a part of brain diseases such as mental illness and addiction. Understanding the role of epigenetics in brain disease may open the door to being able to influence it. This may lead to the development of new and more effective treatments for brain diseases.

A segment from a June 2008 lecture given by Dr. Moshe Szyf, Professor of Pharmacology and Therapeutics at McGill University.

Dr. Szyf talks about studies that looked at epigenetic tags in the brains of suicide victims. He describes some of the laboratory methods scientists use to study epigenetics, and goes over some of the evidence that shows an association between certain epigenetic patterns, suicide, and child abuse.

Scientists are just starting to study how changes in epigenetic tags affect behavior, and how behavior can change epigenetic tags. Some highlights:

Tsankova, N., Renthal, W., Kumar, A., and Nextler, E.J. (2007). Epigenetic regulation in psychiatric disorders. Nature Reviews Neuroscience, 8: 355-367 (subscription required).

Sweatt, J.D. (2009). Experience-dependent epigenetic modifications in the central nervous system. Biological Psychiatry, 65: 191-197 (subscription required).

Kumar, A. et al. (2008). Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48 (2): 303-314 (subscription required).

Ongoing research sponsored by the Centre for Addiction and Mental Health

APA format: Genetic Science Learning Center (2014, June 22) Epigenetics and the Human Brain. Learn.Genetics. Retrieved October 07, 2015, from http://learn.genetics.utah.edu/content/epigenetics/brain/ MLA format: Genetic Science Learning Center. "Epigenetics and the Human Brain." Learn.Genetics 7 October 2015 <http://learn.genetics.utah.edu/content/epigenetics/brain/> Chicago format: Genetic Science Learning Center, "Epigenetics and the Human Brain," Learn.Genetics, 22 June 2014, <http://learn.genetics.utah.edu/content/epigenetics/brain/> (7 October 2015)

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Epigenetics and the Human Brain - Learn Genetics

Aggregates of the SAGA protein Ataxin-7 in Spinocerebellar Ataxia-7 astrocytes. Courtesy of Sean McCullough, graduate student in Dr. Patrick Grant's laboratory.

Research in Epigenetics at UVA focuses on the study of heritable changes in phenotype and gene function that are not caused by direct alterations in DNA sequence.

DNA in eukaryotic cells is packaged into chromatin by histone proteins. DNA-driven cellular processes such as gene expression require alteration of chromatin structure to access this packaged DNA. Epigenetic changes, including chromatin remodeling, histone exchange, or chemical modification of histone proteins, affect access to chromatin DNA. Modifications to the chromatin through processes such as DNA methylation and histone acetylation are being increasingly appreciated as key determinants of cellular phenotype. Epigenetic chromatin modification is also influenced by environmental factors and can be stably transmitted across generations.

Improved understanding of epigenetic processes is producing exciting advances in cancer detection and treatment. For example, epigenetic profiles can improve cancer detection, and new anti-cancer drugs target the chromatin modifying machinery.

The UVA epigenetics research groups utilize model organisms, mammalian cells and human-derived samples in their studies. A variety of experimental approaches, including biochemistry, genetics, genome-wide analysis and bioinformatics, and behavioral studies are being applied to study epigenetic mechanisms and changes associated with human disease.

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Biomedical Sciences Graduate Program | Epigenetics

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What is Epigenetics?

The term epigenetics refers to heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence; a change in phenotype without a change in genotype. Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc. Or, epigenetic change can have more damaging effects that can result in diseases like cancer. At least three systems including DNA methylation, histone modification and non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic change. New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases.

The Evolving Landscape of Epigenetic Research: A Brief History

What began as broad research focused on combining genetics and developmental biology by well-respected scientists including Conrad H. Waddington and Ernst Hadorn during the mid-twentieth century has evolved into the field we currently refer to as epigenetics. The term epigenetics, which was coined by Waddington in 1942, was derived from the Greek word epigenesis which originally described the influence of genetic processes on development. During the 1990s there became a renewed interest in genetic assimilation. This lead to elucidation of the molecular basis of Conrad Waddingtons observations in which environmental stress caused genetic assimilation of certain phenotypic characteristics in Drosophila fruit flies. Since then, research efforts have been focused on unraveling the epigenetic mechanisms related to these types of changes. Currently, DNA methylation is one of the most broadly studied and well-characterized epigenetic modifications dating back to studies done by Griffith and Mahler in 1969 which suggested that DNA methylation may be important in long term memory function. The renewed interest in epigenetics has led to new findings about the relationship between epigenetic changes and a host of disorders including various cancers, mental retardation associated disorders, immune disorders, neuropsychiatric disorders and pediatric disorders.

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Epigenetics: Fundamentals | What is Epigenetics?

Please note that this section contains my personal notes from my readings on this topic.

I first heard about epigenetics on a Dr. Oz show discussing pregnancy myths. He says that this new field of science epigenetics is finding that what happens in the womb can influence which genes are turned on and off. From a PBS special on epigenetics:

Epigenetics literally translates into just meaning above the genome. So if you would think, for example, of the genome as being like a computer, the hardware of a computer, the epigenome would be like the software that tells the computer when to work, how to work, and how much.

Randy Jirtle in Epigenetics on PBS (July 24, 2007)

In fact, its the epigenome that tells our cells what sort of cells they should be. Skin? Hair? Heart? You see, all these cells have the same genes. But their epigenomes silence the unneeded ones to make cells different from one another. Epigenetic instructions pass on as cells divide, but theyre not necessarily permanent. Researchers think they can change, especially during critical periods like puberty or pregnancy.

Neil Degrasse Tyson in Epigenetics on PBS (July 24, 2007)

Basically, what you eat can affect your future generations. So youre not only what you eat, but potentially what your mother ate, and possibly even what your grandparents ate.

Randy Jirtle in Epigenetics on PBS (July 24, 2007)

One of the main findings of our research is that epigenomes can change in function of what we eat, of what we smoke, of what we drink. And this is one of the key differences between epigenetics and genetics.

Manel Esteller in Epigenetics on PBS (July 24, 2007)

From the Dr. Oz website:

As DNA, the blueprint of your body, is rolled out during development, it gets copied. And while that copying occurs, the things you are experiencing what you eat, the toxins you are exposed to can stop that copy machine from working properly. This basic principal of epigenetics means that, while we cant control what genes we pass on to our children, we may be able to control which genes get turned on or turned off.

Heres another example that will help you put epigenetics in perspective. We share 99.8 percent of the same DNA as a monkey, and any two babies share 99.9 percent of the same DNA. Heck, we even have 50 percent of the same DNA as a banana. So genes alone cannot explain the diversity in the way we look, act, behave, and develop. How those genes are expressed plays a huge role in how vastly different we are from monkeys and how explicitly and subtly different we are from each other.

What you can do:

CAN YOU CONTROL WHICH GENES YOUR CHILD WILL EXPRESS?

ByDR. MICHAEL ROIZEN

While you cant control which genes you pass on to your child, you do have some influence over which genes are expressed, affecting what features are seen in your baby (his phenotype). In fact, what you eat, breathe, and even feel can affect the long-term health of your child.

Stressors in the mothers environment cause a change in the gene expression patterns of the fetus. That means the chemicals your baby is exposed to in utero, via the foods you eat and the cigarettes you dont inhale, serve as biological light switches in your babys development. On, off, on, off you decide how your childs genes are expressed, even as early as conception.

You dont have total control. We still dont know how you can change your babys eye color, or when his hair falls out. But we do know how to influence some really important factors like your childs weight or intelligence. So theres an important reason why were able to turn certain genes on and off. Our bodies have to adapt to a changing environment (thats how a species survives, after all). But our ability to adapt would be much too slow if we had to wait generations for our genes to change through random mutation (the classical theory of evolution).

Weve got to get people thinking more about what they do. They have a responsibility for their epigenome. Their genome they inherit. But their epigenome, they potentially can alter, and particularly that of their children. And that brings in responsibility, but it also brings in hope. Youre not necessarily stuck with this. You can alter this.

Randy Jirtle in Epigenetics on PBS (July 24, 2007)

Sources:

(1) Dr. Oz website

(2) Epigenetics on NOVA scienceNOW, Aired on PBS July 24, 2007.

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Epigenetics | The S File -- Pregnancy

Epigenetic regulation refers to biological mechanisms in which DNA, RNA, and proteins are chemically or structurally modified, without changing their primary sequence. These epigenetic modifications play critical roles in the regulation of numerous cellular processes, including gene expression, DNA replication, and recombination. Epigenetic regulatory mechanisms include DNA methylation and hydroxymethylation, histone modification, chromatin remodeling, RNA methylation, and regulation by small and long non-coding RNAs. While epigenetic modifications can be very stable and passed on to multiple generations in some cases, they can also dynamically change in response to specific cellular conditions or environmental stimuli. When epigenetic mechanisms are misregulated, the result can be detrimental to health and can lead to cancer, neurological disorders, and developmental abnormalities. Therefore, epigenetic modifications are emerging as important diagnostic and prognostic biomarkers in many fields of medicine.

In recent years, epigenetics has exploded into one of the most exciting and rapidly expanding fields in biology. Zymo Research has grown with it, becoming The Epigenetics Company. Zymo Research understands the need for high-quality and reliable products for epigenetics research, and we offer an extensive and continually growing line of products, kits, and genome-wide services to facilitate investigations into epigenetic regulation of cellular processes. We are committed to continue meeting the needs of epigenetic researchers into the future.

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Epigenetics Research Technologies

Epigenetics can be defined as acquired changes in chromatin structure that arise independently of a change in the underlying DNA nucleotide sequence. Epigenetic modifications - including acetylation, methylation, phosphorylation, and ubiquitination amongst others - alter the accessibility of DNA to transcription machinery and therefore influence gene expression. Ongoing research is revealing the extent of the influence of epigenetics in disease states, and continues to provide a wealth of novel therapeutic targets.

Epigenetic mechanisms integrate environmental changes at the cellular level and enable cellular plasticity. As a result, they are involved in pathologies related to diet, lifestyle and environmental exposure to toxins, including cancer, inflammation and metabolic disorders. Proteins that carry out these epigenetic modifications can be thought of as being either "writers", "readers" or "erasers".

More Information Epigenetic writers catalyze the addition of chemical groups onto either histone tails or the DNA itself. These modifications are known as epigenetic marks.

More Information Epigenetic reader domains can be thought of as effector proteins that recognize and are recruited to specific epigenetic marks. "Writer" and "eraser" enzymes may also contain such reader domains, leading to the coordination of "read-write" or "read-erase" mechanisms.

More Information Epigenetic marks are not necessarily permanent modifications; instead, they can be removed by a group of enzymes known as "erasers" in order to reverse the influence of a given epigenetic mark on gene expression.

Neuroscience 2015

October 17-21, 2015

Chicago, IL

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Epigenetics | Tocris Bioscience

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Epigenetics - PBS Video

Epigenetics is the study of changes in gene activity which are not caused by changes in the DNA sequence.[1] It is the study of gene expression, the way genes bring about their phenotypic effects.[2]

These changes in gene activity may stay for the remainder of the cell's life and may also last for many generations of cells, through cell divisions. However, there is no change in the underlying DNA sequence of the organism.[3] Instead, non-hereditary factors cause the organism's genes to behave (express themselves) differently.[4]

The best example of epigenetic changes in eukaryotes is the process of cell differentiation. During morphogenesis, generalised stem cells become the cell lines of the embryo which in turn become fully differentiated cells. In other words, a single fertilized egg cell the zygote divides and changes into all the many cell types: neurons, muscle cells, epithelium, blood vessels etc.

As the embryo develops, some genes get switched on, while others are switched off or moderated.[5] This process is called gene regulation. There are many molecules inside the cell nucleus which do the job of adjusting the genes' output.

DNA and histones make up what is called chromatin. Epigenetic modifications to the chromatin are copied during cell division. This produces a line of cells, all of which are alike. This is called a tissue.

Meiosis cancels epigenetic changes, and resets the genome to its baseline state, so the process unfolds in each new generation. There are some exceptions to this rule, but none of these exceptions involve changes to DNA base pair sequences.

This process is different from mutations of the DNA. Genetic mutations change the primary DNA sequence, and mutations can happen in any cell. However, only mutations in cells involved in reproduction can affect the offspring.

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Epigenetics - Simple English Wikipedia, the free encyclopedia