Epigenetics 101

By Susan Gammon, Ph.D.
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Over 400 attendees were recently drawn to Sanford-Burnham’s 35th annual symposium titled “Epigentics: Development and Disease.” So why did so many people come and listen to distinguished scientists and opinion leaders on this hot topic? Well read on to learn that it’s not just the sequence of your DNA that matters!

What is epigenetics?
Epigenetics involves the control of genes through DNA modifications. Epigenetics can determine the fate of a cell by switching genes on or off. Consider the fact that all of your cells have the same DNA, but your body contains many types of cells: neurons, liver cells, blood cells, and muscle cells. How does this happen? In short, cells, tissues, and organs differ because certain genes are “expressed,” and others are “inhibited.” Epigenetic “markers” control the “on/off” switches of genes, but they can have damaging effects that result in diseases like cancer, immune disorders, and neuropsychiatric disorders.

Epigenetic Systems
There are at least three ways that epigenetic control is accomplished:

  1. DNA Methylation: The addition of a methyl (CH3) group to a cytosine nucleotide in DNA.
  2. Histone modification: An alteration in the histone protein(s) that help package and wind the DNA into chromosomes.
  3. Non-coding RNA gene silencing: These RNA molecules regulate gene expression at the transcriptional and post-translational level.

Epigenetics makes us unique
Think about a pair of identical twins. They have exactly the same set of DNA—they are clones of each other. So why don’t identical twins lead identical lives, have identical personalities, and die of the same disease? The cause of this phenomenon is due to epigenetic changes in the human genome, also known as the “epigenome,” that are  acquired by environmental factors.

All sorts of environmental factors and life events can affect the epigenome: diet, exercise, smoking, medicine, and chemicals in the environment. The modification of DNA leads to differences in the expression of genes that contribute to our personality, health, and longevity.

Epigenetics is heritable
In classical genetics theory, the way we live should not alter the basic characteristics of genes. We expect that a fresh, unadulterated, identical set of 30,000 genes is passed from parent to progeny. However, scientists now know that epigenetic “markers” on genes can be inherited.

In animal models of genetic traits, scientists have shown that baby rats of stressed-out mothers are anxious compared to rats born to non-stressed mothers. In this case, the mother’s stress-hormone genes are altered under stress circumstances, and the inherited trait is passed on to the next generation.

A much-cited example in humans is a study involving people living in an isolated community in Northern Sweden whose parents and grandparents gorged themselves during years when an overabundance of food was available. These people had much shorter lives compared to people whose ancestors consistently struggled to get enough food.

Epigenetics is reversible
In the study of stressed-out mother rats giving birth to anxious baby rats (described above), when the anxious rat babies were treated with chemicals that reverse DNA methylation, the negative effects of inadequate maternal behavior were reversed.

In a study of lupus-prone mice, scientists compared the DNA of afflicted mice to normal mice and found distinct epigenetic markers on DNA from mice with the disease. When treated with a molecule called “TSA,” the DNA markers were reversed and the clinical status of the mice improved.

Epigenetics and cancer
Until recently, it was thought that cancer was caused only by abnormalities within genes themselves. Now, researchers have discovered that some types of cancers are caused by epigenetic changes of DNA. Distinct DNA methylation patterns have been associated with breast, colorectal, lung, head and neck, and hematological cancers.

Today, scientists are developing drugs that affect the chromatin structure of nuclear DNA, and the DNA methylation status of genes. Epigenetic markers open new avenues for an early detection, diagnosis, prognosis, as well as therapeutic targets in cancers. The most significant advance in the field of epigenetic therapy is the FDA approved drug “decitabine,” a de-methylation drug that is now the standard of care in myelodysplastics syndrome, a precursor of acute myelogenous leukemia.

Sanford-Burnham and epigenetics
Sanford-Burnham maintains robust research initiatives to further our understanding of the mechanisms and regulation of epigenetics. A sample of our epigenetics research and their area of focus is provided below.

Pier Lorenzo Puri, M.D., Ph.D.
Puri investigates the molecular mechanisms underlying the reprogramming of the genome during cell-lineage commitment. His work includes efforts to discover drugs that promote muscle regeneration to repair diseased muscles such as those found in muscular dystrophy.

Ranjan Perera, Ph.D.
Perera investigates the molecular mechanisms by which non-coding RNA might affect melanoma and prostate cancer in humans. His genome-wide studies have found evidence of abnormal epigenetic processes that lead to abnormal gene expression, suggesting a need for novel therapeutics in these aggressive cancers.

Tariq Rana, Ph.D.
Rana’s laboratory develops and uses innovative approaches to understanding RNA regulation and development of disease. A key area of his research focuses on the epigenetic mechanisms and networks that regulate generation and differentiation of pluripotent stem cells.

Crystal Zhao, Ph.D.
Zhao’s research interest is in understanding the epigenetic regulation of gene expression by large noncoding RNAs in cancer and stem cells. Understanding epigenetic regulation may open windows to therapies that modulate disease-related epigenetic patterns to restore health.

Rui Zhou, Ph.D.
Zhou studies the molecular mechanism governing RNA interference (RNAi) and role of RNAi in anti-viral immunity. Factors associated with RNAi are involved with recruiting factors that modify chromatin—an epigenetic modification that commonly results in gene silencing.

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Susan Gammon, Ph.D.

Susan is an associate director of Communications at Sanford-Burnham.

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