Formation and positioning of nucleosomes: Effect of sequence-dependent long-range correlated structural disorder

Abstract.The understanding of the long-range correlations (LRC) observed in DNA sequences is still an open and very challenging problem. In this paper, we start reviewing recent results obtained when exploring the scaling properties of eucaryotic, eubacterial and archaeal genomic sequences using the space-scale decomposition provided by the wavelet transform (WT). These results suggest that the existence of LRC up to distances ∼ 20-30kbp is the signature of the nucleosomal structure and dynamics of the chromatin fiber. Actually the LRC are mainly observed in the DNA bending profiles obtained when using some structural coding of the DNA sequences that accounts for the fluctuations of the local double-helix curvature within the nucleosome complex. Because of the approximate planarity of nucleosomal DNA loops, we then study the influence of the LRC structural disorder on the thermodynamical properties of 2D elastic chains submitted locally to mechanical/topological constraint as loops. The equilibrium properties of the one-loop system are derived numerically and analytically in the quite realistic weak-disorder limit. The LRC are shown to favor the spontaneous formation of small loops, the larger the LRC, the smaller the size of the loop. We further investigate the dynamical behavior of such a loop using the mean first passage time (MFPT) formalism. We show that the typical short-time loop dynamics is superdiffusive in the presence of LRC. For displacements larger than the loop size, we use large-deviation theory to derive a LRC-dependent anomalous-diffusion rule that accounts for the lack of disorder self-averaging. Potential biological implications on DNA loops involved in nucleosome positioning and dynamics in eucaryotic chromatin are discussed.