Tuesday, 15 May 2012

Epigenetic Change at Heart of Pre-birth Stress Effects

Matthew Roughan

For many years, scientists have been well aware of the links between pre birth stress and ill health later in life. However, until now, the reasons and mechanisms for this link have been unknown. New research out of Japan has proven that there is an epigenetic change that occurs in a cell when stress is applied to it. This means that there is a heritable change in the chromosomes of the cell, without any change in the DNA sequence itself.

Getting into the specifics of it, the researchers found that genes that are usually highly compacted and inaccessible become exposed when they are put under environmental or chemical stress, such as heating or exposure to hostile environments.  These compacted genetic compounds, called heterochromatin, are normally so compact that the machinery inside the cell responsible for genetic transcription and expression can’t get to them, and hence the genes are not expressed. However, it was found that in the stressed organisms, these heterochromatin segments lost their compaction and became more like their more loosely packed relatives, euchromatin, seen in the picture below. Because of this, the genes were no longer protected from the cell transcription machinery, and hence were expressed in the organism’s phenotype.

(Ishii et al, 2011)

You may now be wondering how this Japanese team of researchers came to this discovery. The experimental work was based on the drosophila, more commonly known as the fruit fly. The researchers spliced a specific gene for white eye colour into an area in the chromosome that would usually form part of the heterochromatin, meaning that it would only be expressed if the heterochromatin was disrupted. The results showed that in the control experiments, the white eye gene was silenced, however in the organisms where stress was applied, the distribution of results was close to normal. This proves that the heterochromatin was disrupted, as seen in the picture below.
(Ishii et al, 2011)

This brings me to the point of how and why this disruption of heterochromatin occurs. You may have noticed on the picture that there are a number of proteins and chemicals are drawn impacting on the heterochromatin. The researchers found that the reason the heterochromatin was disrupted was the phosphorylation of a protein called activating transcription factor 2, or ATF-2. It was found that the release of stress induced protein kinases caused the binding of a phosphate molecule with the ATF-2, which in turn caused it to disrupt the heterochromatin. The researchers isolated this altered protein as the cause by running the same experiment with a mutated version of ATF-2, where phosphorylation was almost impossible. In this experiment, it was found that the heterochromatin was unaffected, meaning that ATF-2 was the cause of the epigenetic change.

It was also found that the change in chromatin is inherited by daughter cells. This means that if the gametes are affected, all offspring of the organism will be affected as well. The mechanism for inheritance is not yet known, with the traits not being inherited in a Mendelian manner.

It is very interesting to see exactly how pre-birth stress can affect organisms and their offspring, and hopefully more similar research will be done in the future.

-       Huddleston, J, 2011, ‘Chromatin: the inheritance of stress’, Nature Reviews Molecular Cell Biology, viewed 21st March 2012 <http://www.nature.com/nrm/journal/v12/n8/full/nrm3164.html>

-       Ishii, et al, 2011, Inheritance of stress induced, ATF-2 dependent epigenetic change, Cell, Volume 145, Issue 7, pp. 1049-1061.

-       Reece, et al, 2012, Campbell Biology 9th Edition, Pearson Education: Australia.

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