Dynamic Simulation of active/inactive Chromatin Domains (Dynamische Simulation aktiver/inaktiver Chromatindomänen)

• Antragsteller: Dr. Gregor Kreth
• Fachliche Zuordnung: Biophysik
• Förderung: Förderung von 2003 bis 2006
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5392240

• Erstellungsjahr: 2006

Zusammenfassung der Projektergebnisse

The aim of this work was to see how far a simple polymer model of chromatin would be valid. Using only an AnBm block copolymer model with attractive A and repulsive B segments we was able to show that this leads to secondary structure formation in the form of rosettes. These rosettes were thoroughly investigated. The number of attractive sites was analyzed with respect to the rosette diameter and it was found that 6 to 16 loops of 80kbp to 200kbp produced 1Mbp rosettes of about 300−800nm. Diffusion was also investigated in rosettes of these sizes and it was found that all of the simulated substances diffuse regularly, so the rosette-structure cannot cause anomalous diffusion. Furthermore the accessibility was studied and we found out that 20 − 27nm, i.e. 6kbp to 12kbp of DNA are absolutely inaccessible, depending on the substance. This is direct evidence that structural properties can regulate gene expression and silencing. The next step was to simulate larger structures. Comparing longer simulated domains to two regions of about 3Mbp of the human chromosome 1 yielded astounding agreement. We have shown that the ridge data corresponds to a free polymer chain without any higher order structure beyond the 30nm chromatin fiber. The anti-ridge data corresponded to a ratio of attractive segments of about 30% and thus loop sizes of roughly 120kbp. This is exactly the loop size suggested in the first part of this report. Using the same principles as before, namely only the A n B m block copolymer model, we then simulated an entire human chromosome. The chromosome condensed to about 3.2µm, which is a factor of 1.6 too large compared to experimental values. However, the condensation occurred just by the presence of the attractive sites. No external pressure was imposed on the simulated chromosome. We therefore find it reasonable to assume a greater compaction when the chromosome is surrounded by other chromosomes and bound by a nucleus. Thus the factor of 1.6 may be explained by the lack of external pressure.

Projektbezogene Publikationen (Auswahl)

• Dynamic Simulation of Active/Inactive Chromatin Domains, Europhysics Conference Abstracts, Vol. 28D (2004) (Abstract)
  J. Odenheimer, G. Kreth and D. W. Heermann
  
• Accessibility and diffusion of transcription factor complexes into 1Mbp chromatin domains, Eur. Biophys. J., 34, 637 (2005) (Abstract)
  J. Odenheimer, G. Kreth, D.W. Heermann, R. Martin, C. Cardoso
  
• Int. J. Biol. Phys. 31, No. 3-4 (2005)
  J. Odenheimer, G. Kreth and D. W. Heermann
  
• Int. J. Mod. Phys. C Vol. 16, No. 10 (2005)
  J. Odenheimer, D. W. Heermann, and M. Brill
  
• Modeling of Polycomb-dependent chromosomal interactions involved in Drosophila gene silencing, Biophys. Rev. Lett. Vol. 1, No. 2 (2006)
  S. Ritter, J. Odenheimer, D. W. Heermann, F. Bantignies, C. Grimaud and G. Cavalli