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How Stress is Inherited

Under stressful conditions, a transcription factor in flies turns on genes by releasing its hold on tightly wound DNA, a new study suggests.

By | July 1, 2011

Recent research has shown that stressed parents can pass on epigenetic changes to offspring that influence their risk of disease, but the process behind this transmission remained a mystery. Now, a study published last month (June 21) in Cell shows that when flies are under stress, a transcription factor releases its hold on tightly wound regions of DNA called heterochromatin, allowing them to unravel and be copied.

“The really interesting aspect to the study is that the effects on heterochromatin can be passed on to the kids,” said Oliver Rando, a geneticist at the University of Massachusetts Medical School, who was not involved in the research. The findings echo similar results in yeast, suggesting this molecular pathway for epigenetic inheritance is conserved across species including humans, he added.

Since the 1990s, when David Barker observed that low birth weight babies were more prone to heart disease and diabetes later in life, researchers have suspected that stressful experiences, such as famine, of parents can cause epigenetic changes in their children. But how stress achieved this effect wasn’t clear.

Last year, Rando and his colleagues found that male rats fed a low-protein diet exhibited changes in DNA methylation and higher levels of cholesterol formation in the liver—differences that they then passed on to their young. And a 2009 study in yeast showed that the molecule ATF-1, which normally silences genes by binding to heterochromatin, releases the DNA to allow transcription under stressful conditions. To see if a similar pathway operated in higher life forms, molecular geneticist Shunsuke Ishii and his colleagues at RIKEN in Japan studied ATF-1’s close cousin, a transcription factor called ATF-2 that is found in Drosophila.

In unstressed flies, the transcription factor ATF-2 bound to heterochromatin, causing it to pack tightly and preventing transcription. But when the researchers exposed Drosophila embryos to heat and osmotic changes—high stress for flies—the ATF-2 was bound by a phosphate group, causing it to release its hold on the DNA. That, in turn, “causes the disruption of tight chromatin structure via reducing histone methylation,” Ishii said, and results in the expression of once-silenced genes. . Activating genes within tightly coiled DNA also turned on a gene in a nearby region which codes for white eye color, allowing the researchers to observe gene activation through this unusual phenotype. Not only did flies exposed to heat shock or osmotic stress develop white eyes, they were more likely to have white-eyed offspring, suggesting that the changes in heterochromatin were heritable.

The researchers are planning follow-up studies to determine which genes are regulated by ATF-2 in other species, and which stressors induce their expression, Ishii said. In humans and mice, for instance, heat shock doesn’t stress embryos, but nutritional deficiencies or psychological stresses may play a role instead.

K.-H. Seong et al., "Inheritance of stress-induced, ATF-2-dependent epigenetic change," Cell, doi:10.1016/j.cell.2011.05.029, 2011.

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Comments

Avatar of: Garry Morrison

Garry Morrison

Posts: 1457

July 5, 2011

Epigenetic inheritance may be the key to solving many unexplained phenomena in humans. The concept of cellular memory passed onto offspring may not be as crazy as it appears.

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Posts: 0

July 5, 2011

Epigenetic inheritance may be the key to solving many unexplained phenomena in humans. The concept of cellular memory passed onto offspring may not be as crazy as it appears.

Avatar of:

Posts: 0

July 5, 2011

Epigenetic inheritance may be the key to solving many unexplained phenomena in humans. The concept of cellular memory passed onto offspring may not be as crazy as it appears.

Avatar of:

Posts: 0

July 6, 2011

Interesting! The transcription factor switches back and forth when one is under stress and when he overcomes it. The spirit or the determination or will, whatever you may say, turns the genes off and on.

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Posts: 0

July 6, 2011

Interesting! The transcription factor switches back and forth when one is under stress and when he overcomes it. The spirit or the determination or will, whatever you may say, turns the genes off and on.

Avatar of: N K Mishra

N K Mishra

Posts: 1457

July 6, 2011

Interesting! The transcription factor switches back and forth when one is under stress and when he overcomes it. The spirit or the determination or will, whatever you may say, turns the genes off and on.

Avatar of: seattlesara

Anonymous

July 8, 2011

Apparently Lamarck wasn't entirely wrong...

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Posts: 0

July 8, 2011

Apparently Lamarck wasn't entirely wrong...

Avatar of:

Posts: 0

July 8, 2011

Apparently Lamarck wasn't entirely wrong...

Avatar of:

Posts: 0

August 17, 2011

In animals (livestock) we have noted 'maternal effects' for sometime in quantitative genetics that we could not separate from environmental behavior learned at the side of the dam or something that happened in utero.  Epigenetic modification because of environmental stressors is not entirely new as the field of metabalomics evolves in animal studies.

Avatar of:

Posts: 0

August 17, 2011

In animals (livestock) we have noted 'maternal effects' for sometime in quantitative genetics that we could not separate from environmental behavior learned at the side of the dam or something that happened in utero.  Epigenetic modification because of environmental stressors is not entirely new as the field of metabalomics evolves in animal studies.

Avatar of: Michael

Anonymous

August 17, 2011

In animals (livestock) we have noted 'maternal effects' for sometime in quantitative genetics that we could not separate from environmental behavior learned at the side of the dam or something that happened in utero.  Epigenetic modification because of environmental stressors is not entirely new as the field of metabalomics evolves in animal studies.

Avatar of: DJ@HGEN

Anonymous

September 14, 2011

Yes, but there are limitations of how much can actually be transmitted because of the processes that produce the gametes. With a lot of handwaving: you are more likely to show the consequences of something your grandmother experienced (stress-wise) when she was pregnant with your mum because that is the time when the meioses is already starting. In males this process only starts in puberty.
Of course another class of effects is those that affect the development in-utero as well as the post-natal care. These I would not class as 'inherited' but as maternal effects.  Epigenetics is defined very very broadly and compassed a very wide array of distinct processes that act at different levels of the cellular hierarchy.  The point I'm trying to make is that there is a limited time-window in which 'experiences' could affect the 'epigenetic status' of the DNA that ends up in the gametes

Avatar of:

Posts: 0

September 14, 2011

Yes, but there are limitations of how much can actually be transmitted because of the processes that produce the gametes. With a lot of handwaving: you are more likely to show the consequences of something your grandmother experienced (stress-wise) when she was pregnant with your mum because that is the time when the meioses is already starting. In males this process only starts in puberty.
Of course another class of effects is those that affect the development in-utero as well as the post-natal care. These I would not class as 'inherited' but as maternal effects.  Epigenetics is defined very very broadly and compassed a very wide array of distinct processes that act at different levels of the cellular hierarchy.  The point I'm trying to make is that there is a limited time-window in which 'experiences' could affect the 'epigenetic status' of the DNA that ends up in the gametes

Avatar of:

Posts: 0

September 14, 2011

Yes, but there are limitations of how much can actually be transmitted because of the processes that produce the gametes. With a lot of handwaving: you are more likely to show the consequences of something your grandmother experienced (stress-wise) when she was pregnant with your mum because that is the time when the meioses is already starting. In males this process only starts in puberty.
Of course another class of effects is those that affect the development in-utero as well as the post-natal care. These I would not class as 'inherited' but as maternal effects.  Epigenetics is defined very very broadly and compassed a very wide array of distinct processes that act at different levels of the cellular hierarchy.  The point I'm trying to make is that there is a limited time-window in which 'experiences' could affect the 'epigenetic status' of the DNA that ends up in the gametes

Avatar of:

Posts: 0

September 15, 2011

Epigenetics takes some of the pressure off maternal influences and shows that paternal influences also produce cross-generational effects.  Maybe this will allow scientists to stop blaming mothers eventually.

Avatar of:

Posts: 0

September 15, 2011

Epigenetics takes some of the pressure off maternal influences and shows that paternal influences also produce cross-generational effects.  Maybe this will allow scientists to stop blaming mothers eventually.

Avatar of: guest PhD

Anonymous

September 15, 2011

Epigenetics takes some of the pressure off maternal influences and shows that paternal influences also produce cross-generational effects.  Maybe this will allow scientists to stop blaming mothers eventually.

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