Wednesday, November 6, 2013

The word epigenetics means things imposed “on top of genetics”. But what sort of things?

Imagine a white mouse breeds with a black mouse – say you get three white babies and three black babies. That’s genetics. We can explain that. The black babies inherited a gene encoding the ability to make the pigment melanin, the others got a defective gene, so they are white.

But what if you get some stripey mice like zebras? How do you explain that? All parts of the mouse have the gene that can make black fur but the blackness only occurs in some places. Think of dalmatian dogs, or of giraffes or leopards.

  • Epigenetics is about turning genes on or off. 
  • It’s also about doing this stably; a leopard doesn’t change its spots even if it sheds its fur each year. 
  • So epigenetics is about stable cellular memory that persists after cell division and, in some cases, even through sexual reproduction.
  • Epigenetics, then, concerns the mechanisms that make organisms or parts of organisms look different, despite the fact they have the same genes and are in the same environment.

Epigenetics is the study of heritable changes in gene activity which are not caused by changes in the DNA sequence.

  • If you've seen even a few fictional portrayals of twins, you've probably noticed that the presentation tends to lean toward one extreme or the other. Either the twins are eerily alike (such as the little girls in "The Shining") or remarkably different (such as the dominant and submissive twin gynecologists in "Dead Ringers"). When two human beings look so similar, the things that make them different are just as perplexing as those that make them alike.

  • One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation. During morphogenesistotipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell – the zygote – continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neuronsmuscle cellsepitheliumendothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.

The Future of Epigenetics           

  • While turning off aging and fine-tuning the human genome are pretty awe-inspiring possibilities, epigeneticists are far more interested in discovering ways to treat epigenetic diseases. 
  • As some cancers occur due to the deactivation of tumor-suppressing genes, researchers have worked to develop medications that reactivate them. The drug azacitidine, for instance, treats leukemia in this manner. 
  • Finding just the right parts of the epigenome to treat, however, can be like finding a needle in a haystack. And once researchers find the areas they want to affect, epigenetic drugs aren't all that specific. They might succeed in blocking or unblocking the genes they wanted to treat, but also affect other genes, resulting in potentially dangerous side effects.

  • Stem cells are also of key interest to epigeneticists. By studying the epigenetic changes that determine how cells develop, it may eventually become possible to dictate what tissue type a stem cell will develop into. 

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