Fear Can Be Turned On Or Off Through DNA Modification

In a multicellular organism, the cells have the same set of genetic instructions because of their identical DNA sequence but have different terminal phenotypes, this activity or expression in which the gene influences can be changed through modification of DNA, protein, or RNA to execute a particular function without changing their primary sequences. This study of gene expression regulation is known as epigenetics; it is heritable, self-perpetuating, and reversible.

Based on this system, neuroscientists at the University of Queensland’s Queensland Brain Institute (QBI) have found a possible way to silence the gene that causes us to feel fear.

For the research, they make a special consideration of the protein, ten-eleven translocation 3 (Tet3) and 5-hydroxymethylcytosine (5-hmC), a DNA pyrimidine nitrogen base, which regulates gene expression and stimulates DNA  demethylation. The reason they choose Tet3 is that it can alter chemically modified base (in this case, 5-hmC) into another. The accumulation of 5-hmC with Tet3 makes the genes to be expressed easily, it elevates rapid behavioral adaptation. They find that 5-hydroxymethylcytosine (5-hmC) is highly dynamic in response to fear extinction training.

The experiment was carried out on individual mouse using 5-hmc with High-throughput screening (HTS) of DNA sequencing, it was shown that fear extinction leads to a dramatic genome-wide redistribution of 5-hmC within the infralimbic prefrontal cortex.

According to the paper, extinction learning-induced Tet3-mediated accumulation of 5-hmC is associated with the establishment of epigenetic states that promote gene expression and rapid behavioral adaptation.

Dr. Bredy, who is a senior researcher at QBI, says  “Genes function is not static but dynamic which can be altered by our daily life experiences and emotionally relevant events have a pronounced effect. By understanding the fundamental relationship between the way in which DNA functions without a change in the underlying sequence, future targets for therapeutic intervention in fear-related anxiety disorders could be developed.

This is the first study of its kind that contemplates how fear is controlled by gene and can be turned on or off through modification of DNA. The study also highlights the adaptive significance of changes brought into chromatin landscape in the adult brain.

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