Researchers at Princeton University have used video imaging to capture the process by which “junk DNA” activates genes.
Image Credit: pogonici / Shutterstock
Junk DNA is the non-coding DNA that makes up more than 90% of the genetic material that is not in the form of genes. Although scientists know that junk DNA contains “enhancers” that can turn genes on or off, it is not clear how these DNA segments find and activate a target gene.
Now, Hongtao Chen and colleagues have captured how this happens in living cells. Their video shows an enhancer finding and connecting to a gene to activate it.
The difficulty involved in imaging genetic activity in living organisms has meant that previous studies of enhancers have mainly used non-living cells, which only provides snapshots in time and means important details are missed.
Now, a new imaging technique developed at Princeton has enabled Chen and team to track the position of an enhancer and its target gene in living fly embryos, while also enabling them to see the gene’s activity.
This study provides the unique opportunity to observe in real time how two regions of DNA interact with each other. We can monitor in time where the enhancer and the gene are physically located and simultaneously measure the gene's activity in an attempt to relate these processes."
Michal Levo, Co-author
As reported in the journal Nature Genetics, the video showed that the enhancer and the gene need to make physical contact before transcription can be activated.
The enhancer remains connected to the gene the whole time the gene is active, with gene activity only stopping once the enhancer has disconnected from the gene.
The study also showed that while transcription is taking place, the structure formed by the enhancer and the gene becomes more compact, which suggests that the DNA in that region changes.
A time series of images reveals how a DNA segment known as an enhancer can turn on, or activate, its target gene. The enhancer (blue) must come in close proximity to the gene (green) to turn on gene activity (pink). (Image Credit: Hongtao Chen / Princeton University)
The researchers say that since there can be many genes between the enhancer and the target gene, it is remarkable that enhancers manage to reach the specific target gene at the right time for it to become active.
They think the answer may lie in the way DNA is wrapped within our cells. If DNA were stretched out, the enhancer and gene may be separated by half and inch, but once the DNA is wrapped and packed into a cell, they could be much closer together.
Analysing gene activation is important since it can help researchers understand healthy development and how even very tiny genetic missteps can lead to congenital disease.
The timing of gene activation is also an important factor in the development of cancer and other diseases.
The key to curing such conditions is our ability to elucidate underlying mechanisms. The goal is to use these rules to regulate and re-engineer the programs underlying development and disease processes.”
Thomas Gregor, Co-author