Physical Force Upregulates Gene Expression

Applying a mechanical force that pulls on a cell stretches chromatin, facilitating transcription, scientists show.

Aug 24, 2016
Alison F. Takemura

WIKIMEDIA, HOWARD VINDIPulling on cells can stretch their chromatin, making genes more available to be expressed, researchers reported in Nature Materials this week (August 22).

“[Cells] cannot see or hear, but they can ‘feel’ mechanical forces,” said study coauthor Ning Wang of the University of Illinois at Urbana-Champaign in a statement, adding: “Mechanical signaling is as important as chemical signaling.”

In the cell, DNA resides in the nucleus in a condensed, protein-associated form, called chromatin. Wang and his international colleagues devised a method to visualize the effects of mechanical stimulation on chromatin and, consequently, gene expression.

The scientists inserted into hamster cells a stretch of DNA with evenly spaced LacI repressor-recognition sequences. By also inserting a fluorescently labelled LacI repressor, the team could visualize a few green spots in the chromatin of a live cell. To stretch the cell, the researchers bound magnetic beads to a surface protein. They could then apply a magnetic field to move the bead, and thus tug the cell, with varying force or in different angles. When they pulled, the researchers measured the displacement of the green spots: the more the chromatin had stretched, the farther apart the spots became.

Stretching the chromatin upregulated a reporter gene the team had also inserted, called dihydrofolate reductase. The team visualized the gene’s transcripts with fluorescent in situ hybridization.

Wang and colleagues found that the force propagated through the cell’s actin network. “The actin in the cytoskeleton forms bundles. When the force is perpendicular to the bundles, it’s like plucking violin strings,” Wang said in the statement. “It’s incredibly tense, and the signal is transferred through the cytoskeleton to the nucleus and stretches the chromatin.”

“Doing it the other way, along the string direction, there isn’t much vibration,” he added, “so a force of the same magnitude has less effect.”