A research team drawn from Poland’s Nencki Institute and Spain’s Instituto de Neurociencias de Alicante (INA) recently found that gene expression can be affected by the distribution of space between units of genetic material, packaged as special fibers. This discovery, which came out of their tests using laboratory mice, could potentially bring the medical community one step closer to conquering neuropsychiatric disorders.
By definition, genes consist of DNA that codes for proteins. Inside cells, DNA is stored in structures made by wrapping it around special molecules called histones. The combination of DNA and histones makes a fibrous genetic material called chromatin. It is chromatin that makes up the characteristic X shape of chromosomes.
What the scientists discovered was that in the specialized brain cells known as neurons, shifts in the distribution of space between these chromatin fibers can in fact create disturbances in normal behavior. In order to get a closer look at the composition of proteins wrapped around the cells, researchers used a non-toxic “staining” protein known as green fluorescent protein (GFP), which won the Chemistry Nobel Prize in 2008. The objective was to take a closer look at the condensed regions of chromatin within the neurons, known as chromocenters, as they were lit up with DNA stain.
These findings are particularly valuable to the study of mental health because they introduce the possibility of discovering the genetic makeup of individuals who develop issues such as depression and anxiety, which could eventually lead to groundbreaking advancements in treatment solutions. If chromatin re-structuring can cause behavioral deficits, doctors may one day be able to identify such variances early on and possibly position themselves to take landmark leaps in medicinal science by having a more direct method of treating a class of issues caused by a phenomenon called serotonergic dysfunction.
Serotonergic dysfunction is a way of referring to specific symptom-producing form of mental illness in which signs of the condition can surface in the form of aggression, erratic behavior, and the inability to choose one’s actions. This can result from low levels of serotonin and is associated with cognitive disorders, bipolar disorder, clinical depression, and schizophrenia. This new information also presents the opportunity for scientists who have previously studied what they call “dark matter” (the area within a gene that scientists once thought of as “nothing” but later found to be transmitting signals relevant to genes). These researchers may now have a foundation to build upon in their efforts to identify the source of the genomic output whose origin they have previously been unable to identify. They will now be able to begin with the premise that the spatial distribution between genes is a variable that may dictate the genetic output and form the structure of DNA itself.
The result of the tests showed that when genes are activated or deactivated within the cell, the output that comes from those genes is not determined solely by the chromatin fibers themselves but also by their immediate surroundings. In other words, if DNA is modified by spatial distribution between chromatin fibers within the genes, humans may, after all, be the product of that unique environment created by the space between.
According to Grzegorz Wilczynski, Associate Professor at Nencki Institute, not only could the findings be important to determining the cause of neuropsychological issues such as autism, but the study also provides the prominent possibility of future research that could lead to advancements in the development of modern medicine.
In order to discover these findings, scientists used custom-made software which allowed them to produce a three-dimensional image analysis. The software creates a more detailed rendering, permitting researchers to more clearly identify the spatial distribution variances of the within the genes of chromatin in the nucleus of the mice neurons. They found that in mice where GFP was activated, chromocenters were larger in size and were not very clear, but were instead more “fuzzy.” As research continues, scientists will be able to more clearly define the impact spatial distribution of chromatin fibers has on the expression of these genes.
By Bridgette Bryant
Photo by Nencki Institute of Experimental Biology