Fukuoka, Japan - Researchers at Kyushu University have made a groundbreaking discovery regarding the dynamics of gene activity, revealing how the spatial distance between specific DNA regions influences bursts of gene expression. This study, published on December 6 in Science Advances, utilizes advanced cell imaging and computer modeling to shed light on the intricate mechanisms of gene regulation, potentially paving the way for novel therapeutic approaches to diseases linked to gene expression dysregulation.
Gene expression is a vital cellular process involving transcription, where DNA is converted into RNA, followed by translation into proteins. Precise regulation of this process is crucial for cellular function and response to environmental changes. Traditionally, gene transcription was viewed as a smooth, continuous process. However, advancements in technology have revealed that transcription occurs in short, unpredictable bursts.
Professor Hiroshi Ochiai, from Kyushu University's Medical Institute of Bioregulation, explains, "A gene will randomly switch on for a few minutes, producing large amounts of RNA, before abruptly turning off again. This phenomenon, known as transcriptional bursting, is essential for controlling gene activity in individual cells, influencing processes such as embryonic development and cancer progression."
The researchers focused on the roles of enhancers and promoters—DNA sequences that regulate transcription—and their spatial relationship. While promoters are adjacent to genes, enhancers can be located far away but can still interact with genes through DNA folding.
Using a sophisticated imaging technique called seq-DNA/RNA-IF-FISH, the team captured the spatial dynamics of DNA, RNA, and proteins within mouse embryonic stem cells. Their findings indicated that when the gene Nanog was active, its most distant enhancer was in close proximity, while the enhancer moved further away when the gene was inactive.
Additionally, the team utilized computer modeling to simulate DNA interactions, revealing that active genes experienced prolonged interactions between enhancers and promoters due to increased viscosity from accumulated proteins and RNA. This viscosity slowed DNA movement, allowing for sustained bursts of gene activity.
Ochiai noted, "The modeling suggests that these interactions reinforce transcriptional bursting. The next step is to validate this mechanism within living cells." This research not only enhances understanding of gene regulation but also holds promise for developing targeted therapies for genetic disorders.