Re: News: Epigenetics: Neurons remember because they move genes in space
- Now this is really cool. We've known for a while that chromatin
movement (not just histone modifications) in the nucleus is another gene
expression regulatory mechanism. When a genetic locus moves to the
nuclear lamina, it is (usually) silenced. This mechanism is used quite
often during development for neural fate decisions, but has been thought
to be due to intrinsic chemical signals (including products of other
genes). This research suggests that cues even external to other cells
can "cause" this inter-nuclear movement.
I cannot access the research for 6 months, but I'm trying to get it
sooner. Anyone else on the group have immediate access? I sure would
like a copy sent to clarencew@...
--- In firstname.lastname@example.org, "Robert Karl Stonjek"
>Institute of Experimental Biology of the Polish Academy of Sciences in
> Epigenetics: Neurons remember because they move genes in space
> March 7th, 2013 in Neuroscience
> How do neurons store information about past events? In the Nencki
Warsaw, a mechanism unknown previously of memory traces formation has
been discovered. It appears that at least some events are remembered
thanks to... geometry.
> Neurons are the most important cells of the nervous system. Scientistsfrom the Nencki Institute of Experimental Biology of the Polish Academy
of Sciences in Warsaw have shown that during neuron stimulation
permanent changes are observed with respect to genes' arrangement within
the cell nucleus. This discovery, reported in the Journal of
Neuroscience, one of the most prestigious journals in the field of
neurobiology, is significant for developing a better understanding of
the processes going on in the mind and disorders of the nervous system,
especially the brain.
>observed that a gene may permanently move deeper into the neuron's cell
> "While conducting experiments on rats after epileptic seizures we have
nucleus. Since modification of the geometrical structure of the nucleus
leads to changes in gene expression, this is how the neuron remembers,
what happened", explains Prof. Grzegorz Wilczynski from the Laboratory
of Molecular and Systemic Neuromorphology at the Nencki Institute.
>networks. In order for the neuronal networks to retain traces of stimuli
> Neurons connect with each another via synapses, forming extended
which caused activation, the shape and functioning of individual
synapses has to change. If stimulus trace is to be permanent, changes
are necessary in the expression of many genes located in the cell
nucleus of individual neurons.
>proteins. But the presence of a gene in the DNA does not mean that it is
> Genes are sections of the deoxyribonucleic acid (DNA) chain coding
active. It has been known for the past several years that gene
expression also depends on the environment within the cell. Chromatin
which fills cells contains gene activating or supressing substances.
>social gathering the importance of what you say will have a different
> "This somewhat resembles interpersonal relations. When you attend a
impact depending on the environment. If the environment is favourable,
your opinion will be seized on and reinforced and you will achieve
social impact. If the environment is less friendly, your opinion will be
silenced", explains Prof. Wilczynski.
>expression is decided by the environment, to date have been associated
> In the case of neurons the epigenetic processes during which gene
only with chemical reactions within the chromatin. Research done at the
Nencki Institute has shown that in neurons we deal with yet another type
of epigenetic effects: changes to the spatial structure of the cell's
nucleus resulting in the formation of permanent memory traces. This is
possible for two reasons. First of all because of the presence of the
nuclear membrane: genes can attach or detach from it, which impacts
their expression. The second reason is related to the specific structure
of the cell nucleus.
>domains or territories. Each domain is filled by just one chromosome,
> The nucleus of a cell consists of many globules, called chromosome
which may slightly move within its territory. As a result of such
movement at the meeting points of the neighbouring domains, fragments of
the DNA chains containing the different genes can come in contact. This
leads to silencing of a group of genes or to their expression: formation
of a transcription factory. However, a slight movement of the DNA chain
in any domain changes the situation: the silenced gene unit resumes
activity or the factory stops functioning.
>have already been observed in certain types of cells, among other in
> Changes to the spatial arrangement of genes within the cell nucleus
epithelium cells. Research done at the Nencki Institute has shown that
external stimuli may cause changes within neurons. Moreover scientists
proved that such changes are permanent and create a distinct genetic
memory trace within the neuronal structure - despite no changes recorded
in the DNA chains themselves.
>which is a brain plasticity disorder. During the seizure the activated
> Neurons used in this study came from rats after epileptic seizure,
neurons are places of turbulent gene expression. Scientists from the
Nencki Institute decided to investigate two genes, known as BDNF and
TRKB. In collaboration with the group of Prof. Marek Switonski from the
University of Life Sciences in Poznan, and with Prof. Marion Cremer from
Munich, these genes' location within the DNA chains has been marked
using a substance glowing after stimulation with laser light. Such
preparations of neurons from control rats and neurons coming from rats
after epileptic seizures were analysed under confocal microscope.
>focal plane. Therefore each image represents a sort of flat, thin cross
> "Confocal microscope registers images only in the vicinity of its
section through the preparation. To reconstruct from a set of many such
slices the spatial structure of the cell nucleus and the arrangement of
genes, we needed to design special software. This task turned out to be
difficult since we were working at the limit of the microscope's
resolving power", says Dr Blazej Ruszczycki from the Nencki Institute.
>5000 cell nuclei to determine the location of both genes of interest
> The software took one year to develop. It was used to study more than
with relation to the centres of the nuclei and the nuclear membrane. For
the BDNF gene, a change has been observed in its location of a few
hundred nanometres (one billionth part of a metre); in the control
animals this gene was present near the nuclear membrane or on it in 50%
of the nuclei, while in animals after seizures this value dropped to
>observed that it remains visible for up to several weeks. The conclusion
> "A double drop is a great change in biology. Moreover, we have
is therefore clear: past events are remembered by neurons also thanks to
changes within the architecture of their cell nuclei", observes Prof.
>March 7th, 2013.
> Provided by Nencki Institute of Experimental Biology
> "Epigenetics: Neurons remember because they move genes in space."
> Posted by
> Robert Karl Stonjek