A recently uncovered code within DNA—referred to as “spatial grammar”—offers insights into how gene activities are organized in the human genome.
This significant discovery, made by researchers from Washington State University and the University of California, San Diego, and published in Nature, confirms the existence of a long-theorized hidden spatial grammar within DNA. This study has the potential to transform our comprehension of gene regulation and how genetic variations may influence gene expression during development or disease.
Central to this code are transcription factors, the proteins responsible for regulating which genes in an individual’s genome are activated or silenced. Traditionally considered merely as activators or repressors of gene action, this new research indicates that the role of transcription factors is much more nuanced.
“In contrast to what textbooks state, genuine activators or repressors of gene activity are surprisingly uncommon,” remarked Sascha Duttke, an assistant professor at WSU, who played a key role in the research within the School of Molecular Biosciences, part of the College of Veterinary Medicine.
Researchers realized that most of these activators also possess repressor functions.
“The common assumption is that removing an activator leads to a loss of activation,” explained Bayley McDonald, a graduate student at WSU and a member of the research team. “However, this was only accurate in about 50% to 60% of instances, indicating something unusual was happening.”
Upon further investigation, the team found that the action of many transcription factors depends significantly on their specific locations.
They identified that the arrangement of transcription factors and their relative positioning to the start of gene transcription plays a vital role in determining gene activity levels. For instance, transcription factors can trigger gene expression when situated upstream or prior to the transcription starting point of a gene, but can suppress its activity if located downstream, or after the gene’s transcription start site.
“It’s about the spacing or ‘ambience’ that dictates whether a transcription factor functions as an activator or repressor,” Duttke explained. “This underscores that, akin to acquiring a new language, to grasp how gene expression patterns are embedded in our genome, we must comprehend both its vocabulary and structure.”
With the integration of this newly identified ‘spatial grammar’, Christopher Benner, an associate professor at UC San Diego, believes researchers can achieve a greater understanding of how mutations or genetic variations impact gene expression and contribute to various diseases.
“The possible applications are extensive,” Benner stated. “At the very least, this will transform how scientists approach the study of gene expression.”
