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Jens-Christian Meiners

Publications and source records attributed to Jens-Christian Meiners.

2 recordsLinked to original sources

Protein-mediated DNA Loop Formation and Breakdown in a Fluctuating Environment

Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, which is a common means of regulating transcription, is very much a stochastic process; the loops arise from the thermal motion of the DNA and other fluctuations of the cellular environment. We present single-molecule measurements of DNA loop formation and breakdown when an artificial fluctuating force, applied to mimic a fluctuating cellular environment, is imposed on the DNA. We show that loop formation is greatly enhanced in the presence of noise of only a fraction of $k_B T$, yet find that hypothetical regulatory schemes that employ mechanical tension in the DNA--as a sensitive switch to control transcription--can be surprisingly robust due to a fortuitous cancellation of noise effects.

q-bio.BM

A Generalized Theory of DNA Looping and Cyclization

We have developed a generalized semi-analytic approach for efficiently computing cyclization and looping $J$ factors of DNA under arbitrary binding constraints. Many biological systems involving DNA-protein interactions impose precise boundary conditions on DNA, which necessitates a treatment beyond the Shimada-Yamakawa model for ring cyclization. Our model allows for DNA to be treated as a heteropolymer with sequence-dependent intrinsic curvature and stiffness. In this framework, we independently compute enthlapic and entropic contributions to the $J$ factor and show that even at small length scales $(\sim \ell_{p})$ entropic effects are significant. We propose a simple analytic formula to describe our numerical results for a homogenous DNA in planar loops, which can be used to predict experimental cyclization and loop formation rates as a function of loop size and binding geometry. We also introduce an effective torsional persistence length that describes the coupling between twist and bending of DNA when looped.

q-bio.BM