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Orchestrating the Genome: The Science of Epigenetics


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Oct 13, 2015

Frederic de Sauvage, Ph.D.

Vice President and Staff Scientist, Molecular Oncology, Genentech

 


The DNA in every one of our cells is the same; it contains the genetic code for every organ and cell in our body. But if the DNA in every cell is exactly the same, how do we end up with so many different types of cells? How do skins cells become skin cells and heart cells become heart cells?

Biological Notation

The answer lies in the epigenome, which helps control the genes encoded in our DNA. You can think of DNA like the written score for a beautiful symphony – it contains the music for the entire orchestra, and yet each instrument only plays individual part. Epigenetics serves as the conductor of this orchestra, turning on and off various genes in perfect harmony.

It does this is by controlling how our DNA is organized. In some areas, the genes in our DNA are tightly wound around specific proteins. Chemical tags on top of these proteins determine how tightly wound the DNA is. If it’s really tight, those genes are unreadable, and can’t be turned on. If it’s loose, those genes can be accessed and turned on. It is these chemical tags that make up the epigenome. You can think of them as biological notes on the symphonic score of our DNA.

What’s fascinating about the epigenome is that it can change in response to our environment and behavior. For example, our diet and exercise habits can influence our epigenome, which in turn can turn on and off particular genes in certain organs. This also helps explain why identical twins aren’t actually identical. Their differing experiences lead to distinct changes in their epigenomes, and cause biological differences over time.

And the more we learn about the epigenome, the more important it becomes in helping to explain the differences between diseased and normal cells. Nowhere is this truer than in cancer.

Dissonance and Disease

Like the troubling cacophony that arises when members of the orchestra play the wrong part, aberrant changes in the epigenome can contribute to cancer and other diseases. In fact, when scientists began studying the cancer genome, they found that some of the most frequently mutated proteins were actually those that regulated the epigenome.

This knowledge adds another layer of complexity in cancer research. In a sense, you can think of a tumor as a developing organ that doesn’t know what it wants to be when it grows up. If its epigenome is working properly, it could turn into healthy cells. If not, some of the right genes may not turn on or some of the wrong genes may not turn off, and this could lead to cancer cells.

Reader, Writers, and Erasers

There are three main types of proteins in our epigenetic orchestra, which are referred to as “readers”, “writers” and “erasers”. Writers are proteins that add chemical tags, while erasers remove them. Readers can read these tags, which lead to changes in gene expression.

All three of these types of proteins are involved with human cancers, and importantly, can also be targeted with investigational medicines. This raises the possibility of a new class of potential cancer medicines.

Conducting a Large Orchestra

The science of epigenetics is new and very exciting. It seems that epigenetics may play a big a role in human cancer. Readers, writers and erasers are opening up many new possibilities for drug discovery, and represent a potentially new class of cancer treatment. By targeting the epigenome and following the science, we may be able to bring our genomes back into perfect harmony.


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  • Epigenetics,
  • Behind The Science,
  • Follow the Science

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