Bilateral BBSRC-SFI: Characterization of a novel Polycomb group protein complex and its effects on the plant epigenome

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The DNA in our cells is packaged on proteins called histones. Recently it has become clear that the histone proteins can be modified in many different ways, for example by addition of methyl groups, and that this can affect the activity of genes nearby. These changes in the histone proteins - often termed epigenetic marks - are important not only because they affect gene activity, but also because in some cases they are inherited through cell division. Intense research focus on the histone proteins has revealed that cells contain sophisticated machinery not only to "write" epigenetic marks, but also to read them, i.e. recognise and interpret them to produce an output such as turning a gene off. In addition, there are "erasers" that can remove specific marks and reverse their effects. One of the most important histone writers are the Polycomb group (PcG) proteins, which control many aspects of development in animals and plants and are thought to provide cells with a stable memory of important events. For example, in plants the PcG proteins help plant flower at the right time of year by giving cells a memory of whether or not winter has occurred. During winter the cold temperatures result in certain genes involved in flowering being switched off and the PcG proteins are important in making sure that cells "remember" to keep these genes off when temperatures increase during spring and summer. For a long time it was a complete mystery how PcG proteins caused these stable memories. In the last ten years there have been major advances. In particular, it has been found that a group of PcG proteins, called PRC2, act together as an enzyme which methylates a specific amino acid on one of the four histone proteins that package DNA. Furthermore, technical developments in sequencing mean that we can now identify which genes in an organism are modified in this way, and how this relates to their activity. Because PcG proteins control genes involved in many economically important traits (flowering, seed size, and the viability of hybrids for example) it is important to know how the activity of the PRC2 is regulated.The starting point for the present proposal was our discovery of several proteins, called ALP, which we found from genetic evidence which suggested that they act oppositely to the PcG and are involved in switching genes on. We later found, somewhat to our surprise, that the ALP proteins and the PRC2 PcG proteins act together in a large multiprotein complex. We think that when the ALP proteins associate with the PRC2 proteins they inhibit their activity so that the normal role of PcG in repressing gene activity is overcome. A further surprise was that the ALP1 protein turns out to be related to proteins called transposases which help parasitic elements called transposons to proliferate in plant and animal genomes. Because the ALP proteins are widely conserved in plants, including cereals, we think they could provide a useful tool to alter the epigenetic marks in plants and ultimately to modify useful agricultural traits. In order to do this, we need to know what effect ALP proteins have on PRC2 proteins, which genes they target, and what effects they have on the distribution of epigenetic marks over the genome. We have developed many of the genetic resources necessary to do this in our earlier work. We have also uncovered an unusual effect of ALP proteins on plants ability to perceive winter (the vernalization response) and wish to investigate whether this is a result of ALP proteins altering epigenetic marks at genes important for vernalization.We propose to conduct the research outlined in this application as a partnership between our laboratories at the University of Edinburgh and Trinity College Dublin, respectively. Our two groups have complementary research strengths and expertise and we believe that, as a team, we can successfully address questions that could not be answered by one group alone.