Most people don’t realise the extent of the biochemical and physiological changes that stress causes. Indeed, new research suggests that offspring might even be vulnerable to changes in gene expression brought on by chronic parental stress.

Different external stressors or traumas all appear to trigger a common chain of internal events, which starts off with the activation of a protein called activating transcription factor-2 (ATF-2).

“Environmental stress, psychological stresses, infection stress and nutrition stress can all activate ATF- 2,” explains Shunsuke Ishii, a scientist at the RIKEN Advanced Science Institute in Tsukuba, Japan, whose group first cloned ATF-2 nearly two decades ago.

Eye pigmentation in flies

When flies are exposed to heat stress, they display red eye pigmentation (red column). Offspring of these flies retain this effect (green); if these 2nd generation flies are also heat-stressed (yellow), the effects are still visible in their 5th generation offspring. © Ki-Hyeon Seong 2011

Ishii was inspired by studies in single-celled yeasts which suggested that ATF-2 triggers chemical changes to chromatin, the material formed when DNA wraps around structural (histone) proteins. These changes often affect which genes are expressed, or ‘switched on’.

To investigate the effects of stress, Ishii and his colleagues examined whether or not ATF-2 is associated with epigenetic regulation in the fruit fly Drosophila melanogaster.

In the strain of Drosophila that the researchers chose as their experimental model, stress can affect eye colour. In a normal, unstressed fly, the ATF-2 protein binds to chromatin and causes the colour gene to be silenced, resulting in a white eye. But when flies are exposed to stress from heat or a high-salt diet, ATF-2 is released from the chromatin, which allows the colour gene to be switched on and results in red eye pigmentation.

Since these kinds of changes are often transmitted across generations, Ishii and his colleagues performed a series of experiments in which heat-stressed flies were crossed with unstressed counterparts. Remarkably, offspring from these crosses maintained the red eye pigmentation seen in the stressed parent.

“This shows that the effects of stress can be inherited without DNA sequence change,” says Ishii. These effects are all dependent on ATF-2. The researchers have identified dozens of genes whose activity may also be modulated by this protein during stress response and Ishii hopes to explore the biological significance of this finding in future studies.

“We are planning to identify target genes of ATF-2 and prove the inheritance of their stress-induced expression change,” he said. “This could be correlated with various diseases.”

For further information contact:

Dr Atsushi Miyawaki
RIKEN Brain Science Institute, Wako, Japan