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Workshops

CECAM-Lorentz Joint Workshop: Multiscale-modelling of nucleosomes and their positioning on DNA

January 15, 2018 to January 19, 2018
Location : CECAM-HQ-EPFL, Lausanne, Switzerland
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Organisers

  • Helmut Schiessel (Instituut-Lorentz for Theoretical Physics, P.O.Box 9506, 2300 RA Leiden, The Netherlands)
  • John H. Maddocks (Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland)

Supports

   CECAM

Description

About three quarters of our DNA is wrapped around protein cylinders forming nucleosomes. The location of nucleosome binding is known to be biologically crucial, e.g. to be closely connected to epigenetics via methylation patterns. As the DNA is strongly bent in a nucleosome the affinity of a given stretch of DNA depends on its elasticity and shape as encoded in its letters, i.e. the nucleotide sequence as well as on methylation patterns and other base modifications. (This is unlike in a book where the text that is printed does not affect the elasticity of the paper.) In addition, mechanical cues can also be written on top of genes exploiting the fact that the genetic code is degenerate. This suggests that DNA molecules have evolved mechanically to guide their own packaging on nucleosomes which in turn affects the expression of their genes.

To understand the role of sequence-dependent DNA elasticity in gene expression requires the coordinated effort of many different theoretical and simulation groups with expertise ranging from all-atom molecular dynamics simulations of DNA, building of coarse-grained mathematical models of DNA and nucleosomes up to bioinformatics approaches that study properties of whole genomes, as well as of course actual experimentalists. This is the right time to set such a concerted effort in motion as high quality data are pouring in almost daily ranging from single-molecule experiments up to genome-wide nucleosome cartography for many organisms.