Researchers at the Stowers Institute for Medical Research have come up with a breakthrough study revealing the battle behind regulating the expressions of genes. The study was published online in Genome Research. The research team at the Stowers Institute examined enhancer regions of fruit fly DNA. These regions possibly increase the likelihood of gene expression.
Gene expression and its regulation is a complex process. It comprises of turning genes on or off. Moreover, it is essential for generating specific cells in the body e.g. nerve cells, epithelial cells, and cells making up bones. A single mutation in this natural process could have a disaster on your hands. The study identifies that the process may be more like a battle between two opposing genetic forces. It isn’t as simple as a step-wise assembly of ingredients.
What does the study find?
The researchers discovered that DNA enhancers are involved in an ongoing contest between activation and repression. This contest results in a different epigenetic state of the histone proteins around which DNA is wrapped. The process of activation ignites the addition of acetyl groups to histones. This acetylation causes the histone proteins to lose their grip on DNA enhancers, allowing them to be switched on.
On the other hand, repression removes these acetyl groups, preventing the switching on of the genes. According to the researchers, this balance between forces can shift an enhancer more easily from inactive to active state. Both the fruit fly Drosophila melanogaster and mammals observe enhancer activation and repression. However, repression is much less studied in mammals.
The findings of the study clarify the often misunderstood role of repression in DNA enhancers. Moreover, they underscore their importance during both activity and inactivity. Activation is usually accredited for its role in expression. For example, epigenetically modified enhancers, that are still inactive, have been thought to be poised for future action. However, this study suggests that these equilibrial enhancers may be repressed, lacking a key ingredient for activation.
When two enzymes responsible for acetylation oppose each other, they create ultra-sensitivity under some conditions. In such a case, a little more activation creates a dramatic switch in the enhancer’s activity. This mechanism allows turning on of a gene in some cells, while it is turned off in other cells of the body.
The study mainly focused on the enhancers of genes necessarily specifying the fruit fly body plan. However, the research team drew on knowledge from diverse sources as well. These include,
- Developmental genetics and its mechanistic analyses of DNA enhancers
- Mechanistic studies on histone modifications
- Global genomic analyses using next-generation sequencing
An insight into the study
Using ChIP-seq analysis, the research team generated high-resolution maps of DNA enhancers under different conditions. Their long-term goal was an extensive mapping and understanding of DNA enhancers. Note there are hundreds of thousands of enhancers in the human genome.
Such insightful research provides an understanding of diseases and developmental disorders. These disorders include the ones that especially arise from mutations in the DNA enhancers. This respective study gives us a glimpse into the genetic forces contributing to human evolution.