A Generalized Theory of DNA Loop Formation:Considering the Effects of Binding Topology and Sequence-Dependent Curvature.

[摘要] We have developed a semi-analytic method for calculating the Stockmayer Jacobson J-factor for protein mediated DNA loop formation.Formation of DNA loops on the order of a few persistence lengths are key to understanding many biological regulatory functions.  The binding of LacI protein within the Lac Operon of emph{E. coli} serves as the canonical example for loop regulated transcription.  We use a non-linear rod model to determine the equilibrium shape of the inter-operator DNA loop under prescribed binding constraints while taking sequence-dependent curvature and elasticity into account. Then we construct a Hamiltonian that describes thermal fluctuations about the open and looped equilibrium states, yielding the entropic and enthalpic costs of loop formation. Our work demonstrates that even for short sequences of the order one persistence length, entropic terms contribute substantially to the J factor.  We also show that entropic considerations are able to determine the most favorable binding topology.The J factor can be used to compare the relative loop lifetimes of various DNA sequences, making it a useful tool in sequence design.  We consider sequence-dependent curvature and stiffness effects, including A-tract bends. For nearly planar DNA loops we have computed an effective torsional persistence length, which demonstrates how torsion bending coupling in a constrained geometry affects the conversion of writhe to twist. We provide several experimental predictions for Tethered Particle Microscopy (TPM) and Fluorescence Resonant Energy Transfer (FRET) base on DNA loop topology.We demonstrate the difference between looping with intrinsically straight and intrinsically bent DNA, such as A-tracts.

[发布机构] University of Michigan

[效力级别] Sequence-dependent Curvature and Stiffness

[关键词] DNA Loops;Sequence-dependent Curvature and Stiffness;Stockmayer Jacobson J Factor;Gene Regulation E. Coli;Parallel and Antiparallel Topologies;Writhe Twist;Physics;Science;Physics