The Epigenetics Revolution (44 page)
Read The Epigenetics Revolution Online
Authors: Nessa Carey
Tags: #Science/Life Sciences/Genetics and Genomics
3. The memory is lost in the next generation (the seeds). This is comparable with the way that most changes to the somatic tissues are ‘wiped clean’ in animals so that Lamarckian inheritance is exceptional, rather than common.
So, at a phenomenon level, vernalisation looks very epigenetic. In recent years, a number of labs have confirmed that epigenetic processes underlie this, at the chromatin modification level.
The key gene involved in vernalisation is called
FLOWERING LOCUS C
or
FLC
for short.
FLC
encodes a protein called a transcriptional repressor. It binds to other genes and stops them getting switched on. There are three genes that are particularly important for flowering in
Arabidopsis thaliana
, called
FT
,
SOC1
and
FD
.
Figure 15.1
shows how
FLC
interacts with these genes, and the consequences this has for flowering. It also shows how the epigenetic status of FLC changes after a period of prolonged cold.
FLOWERING LOCUS C
or
FLC
for short.
FLC
encodes a protein called a transcriptional repressor. It binds to other genes and stops them getting switched on. There are three genes that are particularly important for flowering in
Arabidopsis thaliana
, called
FT
,
SOC1
and
FD
.
Figure 15.1
shows how
FLC
interacts with these genes, and the consequences this has for flowering. It also shows how the epigenetic status of FLC changes after a period of prolonged cold.
Figure 15.1
Epigenetic modifications regulate the expression of the
FLC
gene, which represses the genes which promote flowering. The epigenetic modifications on the
FLC
gene are controlled by temperature.
Epigenetic modifications regulate the expression of the
FLC
gene, which represses the genes which promote flowering. The epigenetic modifications on the
FLC
gene are controlled by temperature.
Before winter, the
FLC
gene promoter carries lots of histone modifications that switch on gene expression. Because of this, the
FLC
gene is highly expressed, and the protein it codes for binds to the target genes and represses them. This keeps the plant in its normal growing vegetative phase. After winter, the histone modifications at the
FLC
gene promoter change to repressive ones. These switch off the
FLC
gene. The FLC protein levels drop, which removes the repression on the target genes. The increased periods of sunlight during spring activate expression of the
FT
gene. It’s essential that FLC levels have gone down by this stage, because if FLC levels are high, the
FT
gene finds it difficult to react to the stimulus from sunlight
2
.
FLC
gene promoter carries lots of histone modifications that switch on gene expression. Because of this, the
FLC
gene is highly expressed, and the protein it codes for binds to the target genes and represses them. This keeps the plant in its normal growing vegetative phase. After winter, the histone modifications at the
FLC
gene promoter change to repressive ones. These switch off the
FLC
gene. The FLC protein levels drop, which removes the repression on the target genes. The increased periods of sunlight during spring activate expression of the
FT
gene. It’s essential that FLC levels have gone down by this stage, because if FLC levels are high, the
FT
gene finds it difficult to react to the stimulus from sunlight
2
.
Experiments with mutated versions of epigenetic enzymes have shown that the changes in histone modifications at the
FLC
gene are critically important in controlling the flowering response. For example, there is a gene called
SDG27
which adds methyl groups to the lysine amino acid at position 4 on histone H3, so it is an epigenetic writer. This methylation is associated with active gene expression. The
SDG27
gene can be mutated experimentally, so that it no longer encodes an active protein. Plants with this mutation have less of this active histone modification at the
FLC
gene promoter. They produce less FLC protein, and so aren’t so good at repressing the genes that trigger flowering. The
SDG27
mutants flower earlier than the normal plants
3
. This demonstrates that the epigenetic modifications at the
FLC
promoter don’t simply reflect the activity levels of the gene, they actually alter the expression. The modifications do actually cause the change in expression.
FLC
gene are critically important in controlling the flowering response. For example, there is a gene called
SDG27
which adds methyl groups to the lysine amino acid at position 4 on histone H3, so it is an epigenetic writer. This methylation is associated with active gene expression. The
SDG27
gene can be mutated experimentally, so that it no longer encodes an active protein. Plants with this mutation have less of this active histone modification at the
FLC
gene promoter. They produce less FLC protein, and so aren’t so good at repressing the genes that trigger flowering. The
SDG27
mutants flower earlier than the normal plants
3
. This demonstrates that the epigenetic modifications at the
FLC
promoter don’t simply reflect the activity levels of the gene, they actually alter the expression. The modifications do actually cause the change in expression.
Cold weather induces a protein in plant cells called VIN3. This protein can bind to the
FLC
promoter. VIN3 is a type of protein called a chromatin remodeller. It can change how tightly chromatin is wound up. When VIN3 binds to the
FLC
promoter, it alters the local structure of the chromatin, making it more accessible to other proteins. Often, opening up chromatin leads to an increase in gene expression. However, in this case, VIN3 attracts yet another enzyme that can add methyl groups to histone proteins. However, this particular enzyme adds methyl groups to the lysine amino acid at position 27 on histone H3. This modification represses gene expression and is one of the most important methods that the plant cell uses to switch off the
FLC
gene
4
,
5
.
FLC
promoter. VIN3 is a type of protein called a chromatin remodeller. It can change how tightly chromatin is wound up. When VIN3 binds to the
FLC
promoter, it alters the local structure of the chromatin, making it more accessible to other proteins. Often, opening up chromatin leads to an increase in gene expression. However, in this case, VIN3 attracts yet another enzyme that can add methyl groups to histone proteins. However, this particular enzyme adds methyl groups to the lysine amino acid at position 27 on histone H3. This modification represses gene expression and is one of the most important methods that the plant cell uses to switch off the
FLC
gene
4
,
5
.
This still raises the question of how cold weather results in epigenetic changes to the
FLC
gene specifically. What is the targeting mechanism? We still don’t know all the details, but one of the stages has been elucidated. Following cold weather, the cells in
Arabidopsis thaliana
produce a long RNA, which doesn’t code for protein. This RNA is called COLDAIR. The COLDAIR non-coding RNA is localised specifically at the
FLC
gene. When localised, it binds to the enzyme complex that creates the important repressive mark at position 27 on histone H3. COLDAIR therefore acts as a targeting mechanism for the enzyme complex
6
.
FLC
gene specifically. What is the targeting mechanism? We still don’t know all the details, but one of the stages has been elucidated. Following cold weather, the cells in
Arabidopsis thaliana
produce a long RNA, which doesn’t code for protein. This RNA is called COLDAIR. The COLDAIR non-coding RNA is localised specifically at the
FLC
gene. When localised, it binds to the enzyme complex that creates the important repressive mark at position 27 on histone H3. COLDAIR therefore acts as a targeting mechanism for the enzyme complex
6
.
When
Arabidopsis thaliana
produces new seeds, the repressive histone marks at the
FLC
gene are removed. They are replaced by activating chromatin modifications. This ensures that when the seeds germinate the
FLC
gene will be switched on, and repress flowering until the new plants have grown through winter.
Arabidopsis thaliana
produces new seeds, the repressive histone marks at the
FLC
gene are removed. They are replaced by activating chromatin modifications. This ensures that when the seeds germinate the
FLC
gene will be switched on, and repress flowering until the new plants have grown through winter.
From these data we can see that flowering plants clearly use some of the same epigenetic machinery as many animal cells. These include modifications of histone proteins, and the use of long non-coding RNAs to target these modifications. True, animal and plant cells use these tools for different end-points – remember the orthopaedic surgeon and the carpenter from the previous chapter – but this is strong evidence for common ancestry and one basic set of tools.
The epigenetic similarities between plants and animals don’t end here either. Just like animals, plants also produce thousands of different small RNA molecules. These don’t code for proteins, instead they silence genes. It was scientists working with plants who first realised that these very small RNA molecules can move from one cell to another, silencing gene expression as they go
7
,
8
. This spreads the epigenetic response to a stimulus from one initial location to distant parts of the organism.
7
,
8
. This spreads the epigenetic response to a stimulus from one initial location to distant parts of the organism.
The kamikaze cereal
Research in
Arabidopsis thaliana
has shown that plants use epigenetic modifications to regulate thousands of genes
9
. This regulation probably serves the same purposes as in animal cells. It helps cells to maintain appropriate but short-term responses to environmental stimuli, and it also locks differentiated cells in permanent patterns of specific gene expression. Because of epigenetic mechanisms we humans don’t have teeth in our eyeballs, and plants don’t have leaves growing out of their roots.
Arabidopsis thaliana
has shown that plants use epigenetic modifications to regulate thousands of genes
9
. This regulation probably serves the same purposes as in animal cells. It helps cells to maintain appropriate but short-term responses to environmental stimuli, and it also locks differentiated cells in permanent patterns of specific gene expression. Because of epigenetic mechanisms we humans don’t have teeth in our eyeballs, and plants don’t have leaves growing out of their roots.
Flowering plants share a characteristic epigenetic phenomenon with mammals, and with no other members of the animal kingdom. Flowering plants are the only organisms we know of besides placental mammals in which genes are imprinted. Imprinting is the process we examined in
Chapter 8
, where the expression pattern of a gene is dependent on whether it was inherited from the mother or father.
Chapter 8
, where the expression pattern of a gene is dependent on whether it was inherited from the mother or father.
At first glance, this similarity between flowering plants and mammals seems positively bizarre. But there’s an interesting parallel between us and our floral relations. In all higher mammals, the fertilised zygote is the source of both the embryo and the placenta. The placenta nourishes the developing embryo, but doesn’t ultimately form part of the new individual. Something rather similar happens when fertilisation occurs in flowering plants. The process is slightly more complicated, but the final fertilised seed contains the embryo and an accessory tissue called the endosperm, shown in
Figure 15.2
.
Figure 15.2
.
Just like the placenta in mammalian development, the endosperm nourishes the embryo. It promotes development and germination but it doesn’t contribute genetically to the next generation. The presence of any accessory tissues during development, be this a placenta or an endosperm, seems to favour the generation of imprinted control of the expression of a select group of genes.
Figure 15.2
The major anatomical components of a seed. The relatively small embryo that will give rise to the new plant is nourished by the endosperm, in a manner somewhat analogous to the nourishment of mammalian embryos by the placenta.
The major anatomical components of a seed. The relatively small embryo that will give rise to the new plant is nourished by the endosperm, in a manner somewhat analogous to the nourishment of mammalian embryos by the placenta.
In fact, something very sophisticated happens in the endosperm of seeds. Just like most animal genomes, the genomes of flowering plants contain retrotransposons. These are usually referred to as TEs – transposable elements. These are the repetitive elements that don’t encode proteins, but can cause havoc if they are activated. This is especially because they can move around in the genome and disrupt gene expression.
Normally such TEs are tightly repressed, but in the endosperm these sequences are switched on. The cells of the endosperm create small RNA molecules from these TEs. These small RNAs travel out from the endosperm into the embryo. They find the TEs in the embryo’s genome that have the same sequence as themselves. These TE small RNA molecules then seem to recruit the machinery that permanently inactivates these potentially dangerous genomic elements. The risk to the endosperm genome through reactivation of the TEs is high. But because the endosperm doesn’t contribute to the next generation genetically, it can undertake this suicide mission, for the greater good
10
,
11
,
12
,
13
.
10
,
11
,
12
,
13
.
Although mammals and flowering plants both carry out imprinting, they seem to use slightly different mechanisms. Mammals inactivate the appropriate copy of the imprinted gene by using DNA methylation. In plants, the paternally-derived copy of the gene is always the one that carries the DNA methylation. However, it’s not always this methylated copy of the gene that is inactivated
14
. In plant imprinting, therefore, DNA methylation tells the cell how a gene was inherited, not how the gene should be expressed.
14
. In plant imprinting, therefore, DNA methylation tells the cell how a gene was inherited, not how the gene should be expressed.
There are some fundamental aspects of DNA methylation that are quite similar between plants and animals. Plant genomes encode active DNA methyltransferase enzymes, and also proteins that can ‘read’ methylated DNA. Just like primordial germ cells in mammals, certain plant cells can actively remove methylation from DNA. In plants, we even know which enzymes carry out this reaction
15
. One is called DEMETER, after the mother of Persephone in Greek myths. Demeter was the goddess of the harvest and it was because of the deal that she struck with Hades, the god of the Underworld, that we have seasons.
15
. One is called DEMETER, after the mother of Persephone in Greek myths. Demeter was the goddess of the harvest and it was because of the deal that she struck with Hades, the god of the Underworld, that we have seasons.
But DNA methylation is also an aspect of epigenetics where there are clear differences in the way plants and higher animals use the same basic system. One of the most obvious differences is that plants don’t just methylate at CpG motifs (cytosine followed by a guanine). Although this is the most common sequence targeted by their DNA methyltransferases, plants will also methylate a cytosine followed by almost any other base
16
.
16
.
A lot of DNA methylation in plants is focused around non-expressed repetitive elements, just like in mammals. But a big difference becomes apparent when we examine the pattern of DNA methylation in expressed genes. About 5 per cent of expressed plant genes have detectable DNA methylation at their promoters, but over 30 per cent are methylated in the regions that encode amino acids, in the so-called body of the genes. Genes with methylation in the body regions tend to be expressed in a wide range of tissues, and are expressed at moderate to high levels in these tissues
17
.
17
.
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