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.
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,
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
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.
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
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