Okay. So, in this next lecture, we'd like to think about the next epigenetic modifications we'll talk about. And they are post-translational histone modifications. So, what I mean by that is that after histones are, histone genes are transcribed and translated, the histone molecules can have additional chemical tags added to them. And these are post-translational modifications. They can come in many different types. So, for example, the addition of an acetyl group, a methyl group, a ubiquital group, a phosphoral group, sumoyal group, many of these, many, many different types that can be added to the histone molecules. We're going to focus on histone acetylation and histone methylation, as they are the best characterised of these histone modifications. These modifications tend to occur on the N-terminal tails, almost exclusively occur on the N-terminal tails of the histones, that protrude out from the nucleosome. It's partly because these are the places that are most accessible to the enzymes that lay down these marks and remove the marks. And also, most accessible to other chromatin proteins that come along and bind these modified histone residues. So, in fact, there are a plethora of different places where these histone modifications can occur. More than 50 sites. And some of these sites can be modified with a variety of different residue, different tags. So, for example, acetylation or methylation. So, lysine residues are subject to both acetylation and methylation, although not at the same time. So, although there are four different types of histones, two of each found within the nucleosome, these histone modifications tend to be on histone H3 and H4. And far fewer of them are found on histone H2A and H2B. Although there are still a few that occur there. So, each of these different histone tail modifications are associated with a different function. We won't go through all of these, but methylation, which can occur as a single, which we tend to abbreviate as Me, can occur as a monomethylation, dimethylation, so two methyl groups, or trimethylation, three methyl groups. And it can occur on lysines or arginines in the histone tails. So, we'll refer to these lysines as K, because that's the short version of lysine in amino acid terminology, and the arginines as R. So, the function of this methylation can vary, but it tends to be associated with some sort of function involving transcription. So, transcriptional activation or silencing and is sometimes, at least in terms of the lysine methylation can be associated with a DNA repair. We're going to focus on methylation and acetylation, and particularly their functions in transcription. And we'll touch on very briefly the function of phosphorylation in repair in another lecture. Because there are more than 50 different residues that can be modified, there's a huge number of permutations and combinations, of the different modifications that can all occur at the same time on the one nucleosome. Because there are so many combinations, it's been proposed and we know that they each have different functional outcomes, it's been proposed that this could be called a histone code. So the idea with this is that if we can study what each of these marks, these histone marks are associated with and the combinations that occur within a normal cell, or within perhaps a cancer cell, we should be able to predict what the outcome would be for the transcription at that location or indeed any of those other functions that we've spoken about. And so, this is really one of the goals of the epigenetics field, is to be able to interpret based on the histone modification profile, what it will mean for the cell. With future research, it's also thought that we may be able to understand, therefore, what history the cell has had, so what it was exposed to over time. And this will become clear in later lectures when we talk about how the environment can influence epigenetic state.