The Epigenetics Revolution

^{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.}

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[275].

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 H[276], 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 plants3. 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[277][278].

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[279].

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.

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[280][281]. This spreads the epigenetic response to a stimulus from one initial location to distant parts of the organism.

The kamikaze cereal