How enhancer-promoter contact frequency sets transcription
In plain words
Genes are often switched on by DNA control elements called enhancers located far along the chain, which must come close to the gene. How the frequency of such contacts translates into gene activity is unknown.
Precise statement
For an enhancer-promoter pair at genomic separation $s$, relate contact probability $p_c(s)$ (or contact rate) to transcriptional burst frequency, and identify the mechanism behind the reported nonlinear dependence of expression on $p_c$ (threshold, multi-step activation, or action at a distance through a condensate). Answer: a quantitative model predicting expression across inserted enhancer positions.
What would settle it
Systematic enhancer-repositioning experiments with simultaneous live measurement of contacts and bursting that match one model.
Status in the literature
Enhancer-repositioning experiments (2022) reported a nonlinear dependence of expression on contact probability; its mechanism is unresolved.
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