The Epigenetics Revolution (46 page)
Read The Epigenetics Revolution Online
Authors: Nessa Carey
Tags: #Science/Life Sciences/Genetics and Genomics
At a conference in Cambridge in 2010, the same authors reported that one of the major environmental changes in Iceland from 1820 to the present day was a shift from a traditional diet to more mainstream European fare
12
. The traditional Icelandic diet contained exceptionally high quantities of dried fish and fermented butter. The latter is very high in butyric acid, the weak histone deacetylase inhibitor. Histone deacetylase inhibitors can alter the function of muscle fibres in blood vessels
13
, which is relevant to the type of stroke that patients with this mutation suffer. There is no formal proof yet that it’s the drop in consumption of dietary histone deacetylase inhibitors that has led to the earlier deaths in this patient group, but it’s a fascinating hypothesis.
12
. The traditional Icelandic diet contained exceptionally high quantities of dried fish and fermented butter. The latter is very high in butyric acid, the weak histone deacetylase inhibitor. Histone deacetylase inhibitors can alter the function of muscle fibres in blood vessels
13
, which is relevant to the type of stroke that patients with this mutation suffer. There is no formal proof yet that it’s the drop in consumption of dietary histone deacetylase inhibitors that has led to the earlier deaths in this patient group, but it’s a fascinating hypothesis.
The fundamental science of epigenetics is the area that is most difficult to make predictions about. One fairly safe bet is that epigenetic mechanisms will continue to crop up in unexpected parts of science. A good recent example of this is in the field of circadian rhythms, the natural 24-hour cycle of physiology and biochemistry found in most living species. A histone acetyltransferase has been shown to be the key protein involved in setting this rhythm
14
, and the rhythm is adjusted by at least one other epigenetic enzyme
15
.
14
, and the rhythm is adjusted by at least one other epigenetic enzyme
15
.
We are also likely to find that some epigenetic enzymes influence cells in many different ways. That’s because quite a few of these enzymes don’t just modify chromatin. They can also modify other proteins in the cell, so may act on lots of different pathways at once. In fact, it has been proposed that some of the histone modifying genes actually evolved before cells contained histones
16
. This would suggest that these enzymes originally had other functions, and have been press-ganged by evolution into becoming controllers of gene expression. It wouldn’t therefore be surprising to find that some of the enzymes have dual functions in our cells.
16
. This would suggest that these enzymes originally had other functions, and have been press-ganged by evolution into becoming controllers of gene expression. It wouldn’t therefore be surprising to find that some of the enzymes have dual functions in our cells.
Some of the most fundamental issues around the molecular machinery of epigenetics remain very mysterious. Our knowledge of how specific modifications are established at selected positions in the genome is really sketchy. We are starting to see a role for non-coding RNAs in this process, but there are still multiple gaps in our understanding. Similarly we have almost no idea of how histone modifications are transmitted from mother cell to daughter cell. We’re pretty sure this happens, as it is part of the molecular memory of cells that allows them to maintain cell fate, but we don’t know how. When DNA is replicated, the histone proteins get pushed to one side. The new copy of the DNA may end up with relatively few of the modified histones. Instead, it may be coated with virgin histones with hardly any modifications. This is corrected very quickly, but we have almost no understanding of how this happens, even though it is one of the most fundamental issues in the whole field of epigenetics.
It’s possible that we won’t be able to solve this mystery until we have the technology and imagination to stop thinking in two dimensions and move to a three-dimensional world. We have become very used to thinking of the genome in linear terms, as strings of bases that are just read in a straightforward fashion. Yet the reality is that different regions of the genome bend and fold, reaching out to each other to create new combinations and regulatory sub-groups. We think of our genetic material as a normal script, but it’s more like the fold-in from the back of
Mad
magazine, where folding an image in a particular way created a new picture. Understanding this process may be critical for truly unravelling how epigenetic modifications and gene combinations work together to create the miracle of the worm or the oak or the crocodile.
Mad
magazine, where folding an image in a particular way created a new picture. Understanding this process may be critical for truly unravelling how epigenetic modifications and gene combinations work together to create the miracle of the worm or the oak or the crocodile.
Or us.
So here’s the summary of what epigenetic research will hold in the next decade. There will be hope and hype, over-promising, blind alleys, wrong turns and occasionally even some discredited research. Science is a human endeavour and sometimes it goes wrong. But at the end of the next ten years we will understand more of the answers to some of biology’s most important questions. Right now we really can’t predict what those answers might be, and in some cases we’re not even sure of the questions, but one thing is for sure.
The epigenetics revolution is underway.
Introduction
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. A useful starting point for descriptions of the symptoms of schizophrenia, its effects on patients and their families, and relevant statistics is
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Chapter 1
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8: 505–26; Gurdon (1962)
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Nature
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9
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. Tobi et al. (2009),
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. Kaminen-Ahola et al. (2010).
. Kaminen-Ahola et al. (2010).
Chapter 6
1
. If you want to know more, try Arthur Koestler’s highly readable though exceptionally partisan book,
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. If you want to know more, try Arthur Koestler’s highly readable though exceptionally partisan book,
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8
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Chapter 7
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308: 548–550.
2
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311: 374–376.
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3
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4
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9
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12
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