The human genome is a molecule in action; the strands separate when they are being copied for cell division; DNA has to be carefully packaged to fit inside of cells and then it moves around to accommodate the transcription of active genes, for some examples. Scientists have now revealed intriguing links between genes, DNA packaging, and movement throughout the genome that has an influence on the control and expression of genes. Dysfunction in the movement of individual genes may have implications for a wide range of disorders. The findings have been reported in Nature Communications.
“The genome is stirred by transcription-driven motions of single genes,” noted senior study author Alexandra Zidovska, a professor of physics at New York University. “Genes move differently, depending on whether they are being read or not, leading to complex, turbulent-like motions of the human genome. Understanding the mechanics behind transcription-dependent motions of single genes in the nucleus might be critical for understanding the human genome in health and disease.”
Most human cells carry the genome in their nucleus, which would extend to about two meters (over six feet) if it was fully extended from end to end. But human cells have an average diameter of about ten micrometers, which is 100,000 times smaller than the length of DNA.
A careful system allows this DNA to both be packaged up so it will fit into a nucleus, as well as allowing the cellular machinery that transcribes active genes into RNA to physically fit into the areas where it needs to go. Previous work by this team has shown that DNA can undergo extensive reorganization and remodeling in the nucleus.
Researchers have hypothesized that a molecule called ATP, a common cellular fuel, powers these genomic processes too.
In this study, the investigators zeroed in on RNA polymerase II, a crucial molecule that transcribes DNA into RNA. They analyzed how the motion from one active gene affects movement in other places in the genome of live human cells. Single genes were highlighted using CRISPR, and the researchers mapped the movement of the genome in the nucleus. This data was then analyzed with mathematical tools.
In the video below, courtesy of Professor Zidovska, a single gene is illuminated as a white dot, and its trajectory is highlighted as a colored curve within the flows of genome, noted by arrows.
This work showed that active genes help stir the entire genome, when it is looser. If a gene is being transcribed while the DNA is less compacted, motion is spurred throughout the genome in places where the DNA has less compacted. But when the genome is more compacted, motion occurs regardless of whether genes are being transcribed.
The study authors suggested that inactive genes in regions with low compaction may be more mobile than genes that are active but in areas with high compaction.
“By revealing these unexpected connections among gene activity, genome compaction, and genome-wide motions, these findings uncover aspects of the genome’s spatiotemporal organization that directly impact gene regulation and expression,” said Zidovska.
Sources: New York University, Nature Communications