Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Geometrical, Conformational And Topological Restraints in Nucleosome Compaction along Chromatin Fibers
Chromatin architecture is the substrate for DNA replication, recombination, transcription, and repair in eukaryotic genomes. It is the result of complex hierarchic assembly of nucleosome arrays in a compact structure. Although the nucleosome structure is known in its molecular details, the basic information about the pattern of the organization of nucleosomes in the chromatin fiber is still debated.
The problem of selecting the compact architectures of the chromatin fiber for different linker lengths can be factorized in one in which only orientational parameters are taken into account and the other in which the lengths of DNA linkers are considered. If the conformational equivalence is assumed, the best packing of nucleosomes requires the uniformity of orientational parameters; this condition imposes that the linker lengths can differ by steps of 10bp. This produces quasi-uniform helical conformations where the nucleosome dyad axes are almost perpendicular to the fibre axis. Therefore, the experimental evidence that the nucleosome dyad axis in natural chromatin is nearly perpendicular to the fiber is a result of the ?quasi-conformational equivalence? of the repeating units, even though linker lengths are not strictly equal. We investigate possible molecular models of the chromatin fiber under the condition of compact nucleosome packing suggested by EM findings. Geometrical and topological constraints were analyzed for a large interval of uniform helical structures imposing the minimum distortion of both the nucleosome and DNA linker canonical structures. Compact fiber architectures are mainly stabilized by the close packing of nucleosome cores but restricted by topological conditions to prevent from clashing of linkers as well as entanglements of linker chain. We found that the geometrical features required for compact nucleosomes severely limit the possible chromatin structures. Furthermore, they require a torsional energy cost in account of changes of DNA linker twist. This is particularly relevant in the case of short linkers as in telomers, yeast and neuronal chromatin. Finally, increasing the nucleosome repeat length of an integral number of 10bp introduces a torsional stress due to the slight difference with the periodicity of canonical B-DNA linker, around 10.5 bp/turn. Such a difference amplifies with the lengthening of the DNA linkers and could justify the transition of the chromatin fiber diameter and density as EM images demonstrate.
Dipartimento di Chimica