Apr 16, 2012Science and Technology
Gene regulation more than just on and off

The TATA transcription factorOur understanding of genetic diseases has rapidly advanced. As processing of genetic codes becomes cheaper and easier, the market for individualized genetic testing has also rapidly grown. While recent research has shown that the availability of genetic testing may not be useful for widescale health risk determination, genetic understanding of specific diseases is still crucial.

Since Francis Crick stated the central dogma of molecular biology -- that DNA makes RNA makes protein -- in 1958, we have focused our understanding of genetic disease on the DNA blueprint. Because DNA codes for the protein, this has lead to the understanding that mutations in DNA lead to disease. But, as we learn more about genetics, it is clear that the gene to disease pathway is more complicated than just knowing how the DNA blueprint reads out. Not only does the right protein need to be made, it needs to be made at the right time at the right place in the right quantity. Thus, even if your DNA signals for a correct protein, lack of correct expression can also cause disease.

It has been known for over a decade that transcription factors play an important role in determining when a gene is expressed or not expressed. Because they play such an important role in the expression of genes, alterations in the function of transcription factors have been linked to diseases such as cancer and diabetes.

Leucine zipper type transcription factor in complex with DNA.While we have known about transcription factors for a while, our understanding has been incomplete. It has generally been assumed that these factors work in a simple on (expression) or off (no expression) fashion, but a recent study found that the binding process of transcription factors is much more dynamic

This study, which was led by Jason Lieb and published in Nature, found that binding occurs in a 'treadmilling' state. During this time, no transcription happens until a molecular clutch moves the transcription factor into stable state binding. Once in stable state binding, transcription increases. This means that regulating of gene expression could occur through changing the time between treadmilling and stable binding. The study alters our current understanding of how transcription factors associate with the genes that they regulate. This change in understanding could provide novel approaches to pharmaceutical targeting of transcription factors. 

Science is an ever-changing field of knowledge. As knowledge is gained, our understanding of complex processes increases. As we learn more about genetics, its clear that genetic risk is more complicated than decoding the DNA blueprint. Before the human genomics project, we believed that the DNA would be the secret to all of our genetic diseases. Transcription factors have been known to play an important role in gene expression for over a decade. Traditionally, it has been believed that these factors work in a simple on or off fashion, but recent research suggests that this process is much more complex. Through increased knowledge about this process, we can potentially find better ways to regulate gene expression, which can hopefully lead to potential drug targets for disease.  

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