The sequence-dependent elasticity of double-helical DNA on a nm length scale can be captured by the rigid base-pair model, whose strains are the relative position and orientation of adjacent base-pairs. Corresponding elastic potentials have been obtained from all-atom MD simulation and from high-resolution structural data. On the scale of a hundred nm, DNA is successfully described by a continuous worm-like chain model with homogeneous elastic properties characterized by a set of four elastic

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... nstants, which have been directly measured in single-molecule experiments. We present here a theory that links these experiments on different scales, by systematically coarse-graining the rigid base-pair model for random sequence DNA to an effective worm-like chain description. The average helical geometry of the molecule is exactly taken into account in our approach. We find that the available microscopic parameters sets predict qualitatively similar mesoscopic parameters. The thermal bending and twisting persistence lengths computed from MD data are 42 and 48 nm, respectively. The static persistence lengths are generally much higher, in agreement with cyclization experiments. All microscopic parameter sets predict negative twist-stretch coupling. The variability and anisotropy of bending stiffness in short random chains lead to non-Gaussian bend angle distributions, but become unimportant after two helical turns.