Study uncovers surprising new ‘spatial grammar’ of gene expression Premium

Groundbreaking new work has found the fate of a gene being transcribed depends on the relative location of the transcription factor binding site.

In his quest to understand how each cell of an organism interprets the same genome in a different way, researcher Sascha Duttke wondered whether there might be any undiscovered rules of biology.

The human genome contains information about our development, functioning, growth, and reproduction, and all of it takes up only about 2 MB of space.

“That led us to wonder: maybe some of the magic is in the CD player, too?” Duttke, an assistant professor at the College of Veterinary Medicine, Washington State University, wrote in an email. “In this analogy, the CD is our genome and the CD player is the regulatory machinery,” and the transcription factors are important components in the player.

Transcription factors are proteins that bind to specific portions of the DNA and control the rate at which the cell transcribes genetic information from DNA to RNA. The cell then makes proteins by ‘reading’ the RNA.

Groundbreaking new work by Duttke and his colleagues has shown that the fate of a gene being transcribed depends on the location of the transcription factor binding site relative to the location where transcription begins.

The results, published in the journal Nature, provide insights into how different spatial arrangements of the same transcription factors can have different effects.

The findings can “help filter and refine genomic tools and algorithms that predict gene expression”, which can inform new diagnostic and therapeutic strategies for diseases like cancers caused by mutations in regulatory elements, Meenakshi Ghosh, a structural biologist-turned clinical scientist, said.