Tunable kinetic destabilization governs RNA polymerase passage through a DNA-bound transcription factor

Optical tweezers show that RNA polymerase passage through DNA-bound Egr-1 is delayed in an orientation- and rNTP-dependent manner, with RNAP destabilizing the Egr-1–DNA complex.

• Why it matters: Gene-body transcription-factor binding can create collisions with elongating RNAP, but the kinetic mechanism resolving these encounters is unclear.
• What they did: RNAP arrival was tracked via DNA-fluctuation suppression while force measurements tested for mechanical eviction; RNAP-induced destabilization was modeled with Monte Carlo simulations, and CpG methylation effects were tested.
• The result: RNAP destabilizes Egr-1–DNA within a short structured interaction zone, increasing TF dissociation non-monotonically with distance; CpG methylation shortens Egr-1 residence time and largely removes the TF-dependent delay, enabling passage-time distributions to match simulations.

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