Henry Stewart Lectures Epigenetics 2005.
Epigenetic Control by Histone Methylation.
Thomas Jenuwein, Senior Scientist, IMP Vienna.
I would like to start my lecture by illustrating the problem that I will be discussing,
which is the question whether the information that is stored in
the DNA sequence will be sufficient to allow multicellular development to proceed,
or whether there are additional mechanisms that help to
facilitate and potentiate genetic information.
We now know the DNA sequence of many modern organisms ranging from unicellular organisms,
such as yeasts to the human genome,
and there are around 35,000 genes in
the human genome giving rise to more than 200 cell types.
However, we are still far from understanding what is
the molecular makeup of a stem cell based on a fully differentiated cell,
or how does a young cell differ from an aged cell.
And is all the information that is required to differentiate
these cell types only residing in the DNA sequence
or are there other mechanisms that help to stabilize it?
Now, I would like to highlight this distinction,
by first discussing what the power of genetic control can do,
and this is shown on the left hand side.
Now genetic control involves mutations of the DNA sequence.
These are alterations that are introduced,
and indicated here by the red asterisks.
As such, mutations of the DNA sequence can be stably inherited.
They will be propagated through the germ line,
and if they accumulate and prevent the pairing of homologous chromosomes,
they will also prevent the propagation of the genetic information,
and can define a novel species barriers.
In contrast to genetic control,
epigenetic control does not alter the DNA sequence.
But epigenetic control, rather,
is mediated towards the chromatin template.
The DNA polymer is not presented as a naked molecule in living cells,
but the physiological template is chromatin,
and that is shown by the four nucleosomes around which the DNA polymer is wrapped.
Each nucleosome consists of histone molecules.
These histone molecules have flexible amino-termini,
shown here in black.
They are a variety of epigenetic modifications or
alterations that can impinge on the chromatin structure,
and they range from modifications of the histone termini.
They also include DNA methylation,
shown here by the red hexagon.
They also involve exchange of histone variants,
indicated by the light colored nucleosome,
and many other mechanisms that I will discuss in the course of this lecture.
One of the big questions in epigenetic research is how
stable are these alterations on the chromatin template?
Will they only be propagated in somatic cells,
or can we also identify imprints in the germ line?
And what is it really,
how can they contribute to the variability of this thing,
cellular phenotypes, during multicellular development?
The question of diversity and how the genetic information that is stored in