Epigenetics: The Keeper of the Code

August 12th, 2016 | Posted by admin in Uncategorized

In recent years, attention has increasingly turned away from DNA's code and toward the way that DNA is packaged and the proteins that interact with it.

These so-called epigenetic factors are heritable, reversible, and hugely influential.

Over the past few decades, epigenetics has become a hot scientific topic.

With potential roles in cancer, neuropsychiatric disorders, and immune disorders, it is no surprise that epigenetics is garnering such intense attention.

The way in which genes are expressed is incredibly complex; it requires the infinitely detailed coordination of multiple molecular players.

Epigenetics creates an additional layer of complexity that researchers are only now beginning to understand.

Every cell in our body (except a small few) contains exactly the same DNA. However, not every part of the DNA is active at the same time. A liver cell, for instance, will have different portions of DNA "switched on" to a skin cell or muscle cell.

Epigenetic mechanisms are responsible for ensuring the correct DNA information is expressed in each specific cell type.

Similarly, throughout our lives, certain genes can be silenced or expressed. These fluctuating expression rates can be influenced by a myriad of life events and behaviors - for instance, where we live, environmental pollution, aging, and exercise.

The definition of epigenetics

Over the years, the words "epigenesis" and "epigenetics" have been used to refer to various - and occasionally overlapping - aspects of biology. Fairly recently, a consensus on its meaning has been reached.

In 2008, at a Cold Spring Harbor meeting, the confusion was cleared up once and for all. A definition for "epigenetics" was proposed, discussed, and accepted:

"A stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence."

An organism's phenotype is the complete picture of its characteristics or traits - anything from its bone structure to its biochemical processes, from its behavior to the color of its eyes.

Of course, an organism's phenotype is affected by its genetic code. However, as research into epigenetics has developed and advanced, scientists have discovered that some traits can be developed and passed from generation to generation without any changes in the gene sequence (genotype).

At first glance, this seems like a game-changer, and, it truly is - a change in phenotype without a change in genotype.

Epigenetics research has shown that an environmental factor - living in a smoke-filled environment, for instance - can make changes to certain aspects of the way genes function (but not the base pairs themselves), which are then passed on to future generations.

A movie-based analogy might help understand the role of epigenetics: if we imagine the human life span to be a long movie, the cells are the actors and actresses. DNA is the script, telling the actors what to do. The words in the script are the DNA sequence, and the stage directions in the script that give specific commands to the actors are the genes.

In this scenario, epigenetics is the director. The script can remain the same, but the director has the power to remove certain scenes or sections of dialogue.

The guts of epigenetics

Epigenetic changes alter the way certain genes are activated, but not the sequence of the DNA code. This can occur in a number of ways, and to understand them, it helps to know a little about the molecular structures involved:

Chromatin: The basis of chromosomes

Chromatin consists of protein, RNA, and DNA - it is what chromosomes are composed of. In the nucleus of our cells, DNA and its associated proteins are stored in the form of chromatin.

Any DNA-related processes, like replication, take place while DNA is stored as chromatin, rather than on DNA in its naked form.

Histones: DNA spools

Within chromatin, some of the most vital players are histones; DNA is wrapped and curled around these proteins, allowing it to be packaged and kept in the relative confines of the cell's nucleus. They are often said to resemble spools, with strings of DNA wrapped around them.

Although tightly packed, histones allow DNA to go through replication and repair while maintaining their structure.

Nucleosome: Basic unit of DNA packaging

A nucleosome is the fundamental subunit of chromatin, protecting the delicate strands of DNA. Each nucleosome consists of a core of eight histone proteins and a stretch of DNA.

Unlike most globular proteins, histones have long "tails" that protrude from the nucleosomes. These tail-like structures help hold groups of nucleosomes together and also serve as the canvas for epigenetic influence.

Histone tails can undergo a number of chemical modifications, including acetylation, methylation, and phosphorylation. These epigenetic tail alterations have an effect on the way in which DNA is replicated and repaired.

Histone tails are only one region in which epigenetics can influence DNA processes. For instance, so-called chromatin remodeling complexes can temporarily adjust how condensed chromatin is - the less tightly chromatin is packaged, the easier it is for proteins to access the DNA and carry out replication or other changes.

In short, the way in which a cell activates or reads DNA's code can be modified by changing the way it is packaged. There is no need to tweak the order of the DNA's code to make changes to the organism's phenotype.

These epigenetic mechanisms, including methylation, changes in histones, and nucleosome alterations are heritable and referred to as the epigenome.

Methylation in disease

The most studied aspect of epigenetics is the role of methylation. In brief, methylation is a process where methyl groups are added to DNA; most often, this has the effect of repressing gene transcription (the first step of DNA replication, where DNA is copied into RNA).

A study in 1969 was the first to suggest that methylation of DNA might be important in the functioning of long-term memory. Since then, the importance of methylation and its role in a number of diseases is slowly being understood.

Immune disorders

Evidence has gathered over recent years demonstrating that a loss of epigenetic control over complex immune processes might contribute to autoimmune diseases. For instance, abnormal methylation of T cells has been measured in patients with lupus - an autoimmune disease characterized by inflammation and multiple organ damage.

Other studies have also shown that methylation might be important in rheumatoid arthritis, another autoimmune condition.

Neuropsychiatric disorders

Certain psychiatric, autistic, and neurodegenerative disorders appear to have an epigenetic component involving methylation - in particular, DNA methyltransferases (DNMT), a family of enzymes involved in methylating DNA.

Other studies have found a potential role of methylation in Alzheimer's disease. One study noted that even in the brains of Alzheimer's patients who had not yet developed symptoms, genes associated with Alzheimer's were methylated differently from normal brains.

A role for methylation in autism has also been posed. Autopsies of autistic brains revealed a deficiency in MECP2 (methyl CpG binding protein 2), a member of a family of proteins that bind to methylated DNA and activate them.

Epigenetics and cancer

Cancer is known to have a strong genetic component. It is now thought that epigenetic factors have a deep involvement and influence over various aspects of its progression.

In 1983, cancer was the first human disease to be linked to epigenetics. The researchers found that genes within colorectal cancer cells were significantly less methylated than normal tissue.

It is now known that too little methylation can create instability in chromosomes and activate oncogenes; and too much methylation can initiate silencing of the genes responsible for suppressing tumors.

Because epigenetics involves reversible changes to aspects of chromatin, our understanding of its role in various diseases could lead to innovative new treatments. A study published in Carcinogenesis in 2009 says:

"The fact that epigenetic aberrations, unlike genetic mutations, are potentially reversible and can be restored to their normal state by epigenetic therapy makes such initiatives promising and therapeutically relevant."

Epigenetics, as a field of study, is still in its infancy. Because of its wide-ranging influence in health and disease, findings from the research that it spawns is likely to be insightful. Only time will tell how much influence epigenetics has over us and our offspring, and how much influence medical science will eventually have over it.

Written by Tim Newman

The original article can be found on Medical News Today.

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Source: Healthy Living Huffington Post

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