Histone dynamics, heritability and variants

Published on October 1, 2007 Updated on February 4, 2014   38 min

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0:00
In this talk, I'd like to discuss with you the issue concerning histone dynamics, their heritability, and their existence in the form of variants.
0:12
DNA in the nucleus is present in the form of chromatin, and that consists of a complex together with proteins. The main proteins found in chromatin are called histones. They are small, basic proteins called H3, H4, H2A, and H2B for the core histones and H1 for the linker histone. They ensure the compaction of DNA in the nucleus. In the human cells about 2 meters of DNA will fit in a volume of about a few micrometers for the diameter of common somatic cells. And this is represented here with a tennis ball on the right-hand panel. So that will impose a problem of accessibility to the DNA for all DNA transactions, which thus necessitates dynamic properties in order for all the metabolic pathways of the DNA level to operate. The additional aspect that histones can bring in the chromatin organization is a source of information. Indeed, this organization can contribute to a differential use of genetic information provided by the DNA and thus, ensure a functional diversity in the different cells. Then the question that ensues is, how is it established, and how can it be inherited? If we now come to compaction,
1:36
which is the first aspect I wanted to present, in the chromatin organization as depicted by this watercolor, which was drawn by Nicolas Bouvier from the ?"???? you can see that there are different levels that ensure this compaction in the nucleus. First, you have the DNA in the form of a helix, which is wrapped around the core histones to form the nucleosome—the sort of tennis ball that was represented before— which then folds up further to give chromatin fibers, which further fold up and then organize in the nucleus to form different domains. So this high level of compaction is dynamic, and the enzymes that have to get access to DNA have to deal with this kind of organization. So if we get back to the DNA helix
2:31
and concentrate on the nucleosomes, as shown here, what is it? The nucleosome consists of DNA, which is wrapped around a core particle—146 base pairs of DNA— around this histone core octamer with one tetramer of H3 and H4 added with two dimers of H2A and H2B.
2:59
This organization is now really appreciated as an important source of information, which is the second aspect that I wanted to put forward in my presentation. Indeed the histone code hypothesis is putting forward the possibility to use the histone modification at various places, mostly in the terminal tails, which are targets of post-translational modifications. And as is indicated on this scheme, you have thus a large repertoire of information with acetylation on lysine, methylation on arginine, methylation on lysine again, phosphorylation on serine, ubiquitination on lysine, and this can operate in combination. And in addition you also have to take into account the fact that histones exist as different variants. One example can be provided with histone H3, and we'll get back to this later on. What is certainly important to point out is that this combination of modification and these different types of variants, which can bring this important source of information are also known as being used for a specific type of information. One example is provided with the trimethylation on lysine 9 of histone H3, which is generally considered as a characteristic mark of a transcriptionally inactive region. Thus we have to understand how this organization and these modifications are imposed to form nucleosomes. So if we get back to the drawing
4:36
that I had put forward initially and get back to the idea of compaction, this means that we have to deal with chromatin dynamics in order for the DNA to be accessible during development. This would be certainly crucial during the cell cycle when the DNA has to be replicated, segregated between the daughter cells, and also during various DNA transactions for DNA repair, recombination, and so on and so forth. If we now talk about the importance of these modifications and this organization that brings about an information the issue of heritability has to be taken into account if you want to faithfully maintain or duplicate both the genetic information, which is provided by the DNA, and the epigenetic information, which is brought about at least in part by this aspect of chromatin organization from the nucleosome up to the organization in the nucleus. So first, if we consider the basic unit, the nucleosome. How do you make this up and how do you make it dynamic? So the dynamics of such an organization
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Histone dynamics, heritability and variants

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