%0 Journal Article
%T Basis of gene-specific transcription regulation by the Integrator complex.
%A Sabath K
%A Nabih A
%A Arnold C
%A Moussa R
%A Domjan D
%A Zaugg JB
%A Jonas S
%J Mol Cell
%V 84
%N 13
%D 2024 Jul 11
%M 38906142
%F 19.328
%R 10.1016/j.molcel.2024.05.027
%X The Integrator complex attenuates gene expression via the premature termination of RNA polymerase II (RNAP2) at promoter-proximal pausing sites. It is required for stimulus response, cell differentiation, and neurodevelopment, but how gene-specific and adaptive regulation by Integrator is achieved remains unclear. Here, we identify two sites on human Integrator subunits 13/14 that serve as binding hubs for sequence-specific transcription factors (TFs) and other transcription effector complexes. When Integrator is attached to paused RNAP2, these hubs are positioned upstream of the transcription bubble, consistent with simultaneous TF-promoter tethering. The TFs co-localize with Integrator genome-wide, increase Integrator abundance on target genes, and co-regulate responsive transcriptional programs. For instance, sensory cilia formation induced by glucose starvation depends on Integrator-TF contacts. Our data suggest TF-mediated promoter recruitment of Integrator as a widespread mechanism for targeted transcription regulation.