Study Shows Gene Arrangement Controls DNA Folding and Expression

Researchers at the Massachusetts Institute of Technology (MIT) have discovered that altering the arrangement of genes, or “gene syntax,” could create circuits that synergize to maximize output. The study found that when a gene is activated, it changes the physical structure of nearby DNA, creating ripple effects that can either boost or suppress neighboring genes.

The team found that DNA becomes looser upstream of an active gene and more tightly wound downstream, affecting how easily other genes can be accessed. By testing different types of syntax (tandem, divergent, and convergent), the researchers observed how these biophysical changes impact gene activity.

The researchers engineered gene circuits containing two genes arranged in tandem, divergent, or convergent configurations and induced stem cells which can differentiate into many other types of cells (pluripotent). The results confirmed their predictions, showing that divergent arrangements boosted expression of both genes, while tandem setups suppressed downstream genes, with effects reaching up to a 25-fold increase or decrease in gene expression and spanning distances of up to 2,000 base pairs between genes.

Using a high-resolution genome mapping technique called Region Capture Micro-C, the researchers found that DNA downstream of an active gene becomes tightly twisted into structures known as plectonemes, making it harder for RNA polymerase to bind and activate nearby genes. To better examine this effect, they used a newly developed system called STRAIGHT-IN Dual, which enables efficient insertion of two genes into the same DNA strand. The findings could help scientists design more precise and efficient synthetic gene circuits for applications in gene therapy and biotechnology.

For more information, read the article from MIT News.