New technique can locate genes’ on-off switches

All the cells in an organism carry the same instruction manual, the DNA, but different cells read and express different portions of it in order to fulfill specific functions in the body. For example, nerve cells express genes that help them send messages to other nerve cells, whereas immune cells express genes that help them make antibodies.

In large part, this highly regulated process of gene expression is what makes us fully functioning, complex beings, rather than a blob of like-minded cells.

At any given time, only a subset of the genes in a given cell are expressed or “turned on.” Proteins called transcription factors act as the molecular switchboard operators of the cell, binding specific sites in the DNA to flip different genes on and off. Despite their importance, researchers still have difficulty identifying these transcription factor binding sites.

Recently Stowers scientists reported the development of a new method called ChIP-nexus that can precisely and reliably map these sites, vastly outperforming previous techniques. Stowers Associate Investigator Julia Zeitlinger, PhD, who led the study, explains that researchers can use the new method to understand how transcription factors interact with DNA to control gene expression. For example, the technique has already shown that transcription factors’ binding sites are not scattered across the genome as previously thought, but rather appear in specific, predictable sequences.

Zeitlinger thinks the technique represents an important step forward for the field and will ultimately supplant other methods of studying gene regulation.

This report was published in the March 9, 2015, issue of Nature Biotechnology.