So if we consider some of the things that we'll talk about in terms of environmental effects on epigenetic control, we're going to spend probably the most time thinking about how our diet can influence epigenetic control. We'll think about some human examples of how diet appears to have, may have altered epigenetic control in instances of feast or famine. And then we'll go through a number of examples involving the mouse where we know that their diet has altered the availability of various substances. We'll also think more specifically about paternal effects. So effects that has passed down through the father's line. And these paternal environmental effects, both in humans and in models. And we'll finally think about an example of maternal care. So where the mothering style seems to influence epigenetic control. So it's nice at this point to consider, what do we know? What's the evidence in non-mammalian examples, although our, the focus of this course is on mammalian examples. What do we know about how the environment can alter epigenetics in other organisms. So in turtles, instead of having sex determined or gender determined by X and Y chromosomes, so genetic determination as we have in mammals. In turtles, males and females are genetically identical. So the way that turtles determine sex is instead by the temperature at which the egg is incubated. So we know that, we've probably all seen videos of very large clutches of turtle eggs being buried in the sand on the beach. And it depends on what temperature that egg within the context of these pile of eggs that the egg is exposed to. And that will determine whether or not you'll get a female or a male turtle at the other end. So this temperature dependence and not a genetic dependence as I said they're genetically the same, males and females. Suggest that there's probably some epigenetic involvement here in sex determination in turtles. If we think back to plants, we know many plants actually need a period of cold in order for them to flower the next spring. And so here's a picture of some beautiful tulips. And this is one really good example. So bulbs, many bulbs need to have an exposure to cold, although other flowering planets as well for them to be able to flower in the spring. So this isn't always obvious to people that live in very cold climates, but those of us that live in Australia especially in the warmer cities in Australia know you have to dig your bulbs up at the end of spring each year after they've flowered and put them in the fridge over summer. Plant them again in autumn otherwise you won't get a flower the following year. So this, this process is called vernalisation. And it's actually now quite well characterised epigenetically, and we know it involves many epigenetic modifications that we've spoken about over the previous weeks. Particularly, the polycomb repressive complex two. So these are two examples of how temperature can alter epigenetic control in non-mammalian species. We also know that diet can influence epigenetic control in honeybees. So here's a picture where the lower bees, the smaller bees that are slightly more stripy, are the worker bees. And you can see the nice, big fat queen bee. These bees are genetically identical, so the only reason you get a queen bee is that she ate royal jelly. There's a change in her diet. And yet there's a very big phenotypic consequence. A queen bee looks distinctly different to a worker bee, and this is the same for the lifetime of that bee. So this is one instance where diet absolutely influences epigenetic control in this case as I said they're genetically identical but have a different outcome. They're epigenetically different. So clearly in this lower organism the bee we know diet can influence can influence epigenetics. So if we turn now to thinking about mammals, before we go into specific examples in later lectures, I'd like to bring up some of these, the key concepts that we need to think about while considering the influence of the environment on epigenetic control. But also the potential that any environmental change could be trans-generationally heritable, in other words passed on to the offspring for several generations to come. So the first thing that we want to think about is that there are sensitive periods when the environment may be able to influence epigenetic makeup. So it's not necessarily true that altered environment at any stage of development could actually in a different phenotype or a different epigenetic outcome. So if we think about this in terms of this figure that I've shown you many times now of epigenetic reprogramming. The periods that are actually sensitive to epigenetic control are those that are the same ones that were sensitive when we talked, we spoke about assisted reproductive technologies or IVF. So, the period of primordial germ cell development all the way through to the production of mature eggs and sperm seems to be one sensitive period. The second sensitive period is the pre-implantation period and early post-implantation period, shown here, and both of these periods you'll remember are periods of active remodelling of the epigenome. So it seems that at these times when we have this active reprogramming, we have removal and then laying down of epigenetic marks at different places in the genome but in general in the genome as a whole. These are the periods when we seem to, that they seem to be most sensitive to changes in the environment. So, in what we spoke about in week four, the change in the environment was taking out an oocyte in the sperm and allowing fertilisation and development to happen in a dish. This of course is a major change in the environment. Or other changes in the environment, for example, changes to the diet can also influence these critical time periods it would appear. However when we're in this somatic maintenance period as we are for most of our lives in fact then this seems to be less sensitive. Now of course I'm making generalisations here. We have these two major periods of epigenetic reprogramming throughout the genome. Of course when you go through tissue-specific differentiation for each of the organs that we think about in the adult. There are brief windows in time when particular organs will have a very sensitive period as well, because of how that particular organ develops. But they're not as sensitive perhaps in terms of the whole organism as these other periods, these two periods of germ cell development and early embryonic development. Okay, so this is what we're talking about when we talk about sensitive periods. When is the environment changing, and at what periods are they affecting these so called sensitive periods? The second concept that I'd like to talk about in this first introductory lecture for this week is again transgenerational epigenetic inheritance through the gametes. So, over the past decade or so, there's been a lot of discussion in the literature about transgenerational epigenetic inheritance. And that's because it's really a fascinating topic. If you think about it, what this is implying is that you'll inherit some phenotype or pattern of gene expression from your parent or grandparent. And this will be passed through not because of a genetic change in your DNA, which we all know we inherit from our parents and obviously from our grandparents as well, but rather because presumably of some epigenetic change. So this passing from parent to offspring of something other than the genetic information. Really goes against what we think of as being the way that inheritance works. And so, this is why it is so tantalising to think that this might actually happen in, and also it changes the way we really think about the inheritance of phenotypic traits. And so there's been a lot of interest. But over the last few years in particular, it's become a very hot topic to think about whether this is truly transgenerational epigenetic inheritance through the gametes. What this means is that rather than it being because of any other effect, this actually is because of some transmission of epigenetic information through the germ line. So it really suggests that perhaps some parts of the genome have been incompletely cleared during epigenetic reprogramming. This is one model by which it can happen. We're going to come back to this again at the end of this week, once we've considered some of these examples that might, might involve transgenerational epigenetic inheritance through the gametes. So in other words, if this does happen, how does it happen? How can you have a region of the genome perhaps carrying this epigenetic marks and being passed through the germ line. Do they escape all of that epigenetic reprogramming that we've spoken about? The other model where there's also some evidence for is that perhaps they don't escape this global epigenetic reprogramming. But rather, there is some sort of messenger molecule and this messenger molecule might be the molecule that itself is found in the germ cells and being transmitted through the gametes but that will then lead on to the establishment of different epigenetic marks. So these are quite detailed concepts and ones that we'll just come to, as I said, for a brief period at the end of this week's lectures. But I think that really the reason that we want to think about them and the reason that we want to make a distinction between transgenerational epigenetic inheritance through the gametes, and other influences on epigenetic, what would appear to be epigenetic inheritance is because it changes the way that we really think about. These mechanisms and it changes the way that we might be concerned if whether the environment would have an effect. So, there are other effects which may appear like transgenerational epigenetic inheritance but rather than through the gametes. But actually rather than being that are due to some sort of altered maternal care and if you setup a particular state because of maternal care after birth. This may then lead to a mothering style which is mimicked by the offspring. This is not the same thing. And we'll think about these different altered sort of options, if you like and what they mean. So in the next lecture, what we'll start to do is start thinking about human examples of when the environment appears to alter epigenetic control and the data that's there for these examples.
