Mihaela van der Schaar

Using DEFT, an LLM-guided interpretable decision-tree framework, the authors found that pause sites are discriminated by a G at the pause position, C or T at +1 and a minimum G content in the 49 upstream bases (held-out AUROC 0.92, accuracy 0.87); inserting a 377 bp G-less cassette at the 5' ends of NDRG1 and HSP90AA1 abolished the promoter-proximal pause in an orientation-dependent way without impairing hypoxic or heat-shock activation (NDRG1 was even super-activated), while ChIP 5' RNAPII, Ser5P and NELF peaks persisted without NET-seq-detectable pausing and CTD deletion weakened the pause and shifted its peak from ~+80 to ~+40, supporting a model in which the pause is initiated by G-dependent arrest and stabilized by factors including CTD-mediated tethering.

Using DEFT, an LLM-guided interpretable decision-tree framework, the authors found that pause sites are discriminated by a G at the pause position, C or T at +1 and a minimum G content in the 49 upstream bases (held-out AUROC 0.92, accuracy 0.87); inserting a 377 bp G-less cassette at the 5' ends of NDRG1 and HSP90AA1 abolished the promoter-proximal pause in an orientation-dependent way without impairing hypoxic or heat-shock activation (NDRG1 was even super-activated), while ChIP 5' RNAPII, Ser5P and NELF peaks persisted without NET-seq-detectable pausing and CTD deletion weakened the pause and shifted its peak from ~+80 to ~+40, supporting a model in which the pause is initiated by G-dependent arrest and stabilized by factors including CTD-mediated tethering.