New insights into how gene transcription influences genome motion
· News-MedicalA team of scientists has discovered surprising connections among gene activity, genome packing, and genome-wide motions, revealing aspects of the genome's organization that directly affect gene regulation and expression.
The findings, reported in the journal Nature Communications, bolster our understanding of the mechanics behind transcription-dependent motions of single genes-;the dysfunction of which may lead to neurological and cardiovascular disorders as well as to cancer.
Alexandra Zidovska, professor of physics at New York University and senior author of the studyThe genome is 'stirred' by transcription-driven motions of single genes. 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."
However, the origin of these motions is little understood. Scientists have hypothesized that molecular motors fueled by adenosine triphosphate (ATP) molecules, which provide energy for many biological processes, are the drivers. These active motors are thought to apply forces on DNA, which can lead to a motion of DNA and the nucleoplasm-;its surrounding fluid. But the larger physical machinations behind it remain elusive.
With this in mind, Zidovska and her colleagues focused on RNA polymerase II-;responsible for the transcription and one of the most abundant molecular motors in the cell nucleus. When a gene is active, i.e. actively transcribed, the responsible molecular machinery applies forces on DNA during its processing.
In their study, the researchers initially examined the motions of the genes-;when they are inactive-;then "switched" these genes on and observed how their motion changes once "active." At the same time, the authors used DCS to map flows of the surrounding genome, monitoring how the genome flows across the nucleus before and after gene activation.
"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," says Zidovska.
The work also adds to our understanding of physics.
"This research provides new insights into the physics of active and living systems," she observes. "By revealing an emergent behavior of active living systems, such as the human genome, it teaches us new physics."
This research was supported by grants from the National Institutes of Health (R00-GM104152 and R01-GM145924), the National Science Foundation (CAREER PHY-1554880, PHY-2210541, and CMMI-1762506), and a New York University Whitehead Fellowship for Junior Faculty in Biomedical and Biological Sciences.
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