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Wednesday, 27 March, 2013

Our Genome - always on the move

Statistical model for the assembly of nucleosomes

In a living cell, everything is in motion. This is done both actively -through specific organizational changes by proteins which consume energy- as well as passively, when particles absorb thermal energy from the environment and convert it into small undirected movements. And this general principle holds down to the level of our genome.

Accordingly, Prof. Ulrich Gerland and his colleagues at the Chair for Theoretical Biophysics at LMU have developed a model that accounts for the stochastic distribution of “packaging” proteins, along our DNA. They are responsible for the “first level” packaging, in which the DNA strand is wound in spool-like shapes around complexes of histone proteins (see Fig.) Such a stretch of DNA with histones together is called a nucleosome. The distances between the nucleosomes are not fixed, but the DNA slides more or less on the histone. In doing so, end segments of the DNA oftern become temporarily unbound from the histones, experts call this effect "nucleosome breathing".


Test-Piece: yeast DNA

Through such processes, the arrangement of the random nucleosomes is different in each individual cell. When one averages over many cells, however, a remarkably regular pattern emerges. As a basis for the the Munich physicists' computational model, they use the entire genome of twelve different yeasts. Using the model, they have successfully provided a quantitative description of nucleosome assembly patterns for the experimental data provided by their co-authors from biochemistry. Comparison of the patterns indicates that the nucleosome arrangements differ in different yeasts. By introducing the concept of nucleosome breathing, however, the individual samples can all be explained within the same "unified" physical model.


Yet unknown function

What exactly is behind the phenomenon of the "breathing nuclesomes" is not precisely known, explains Gerland, "We do not know whether the arrangement generally serves a biological function or whether it is primarily a byproduct of mechanisms that read and edit the genetic information. However, it is known that the exact position of certain nucleosomes is crucial in determining whether the genetic information is read in a gene or not." In any case, the unifying physical model will be a valuable basis for further studies that seek to quantitatively understand the molecular processes which control the readout process of genetic information.

 

Link to Gerland Group


Publication:

Toward a unified physical model of nucleosome patterns flanking transcription start sites. Wolfgang Möbius, Brendan Osberg, Alexander M. Tsankov, Oliver J. Rando, and Ulrich Gerland. PNAS March 18, 2013 (online)

Link to Publication

 

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