{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318299/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318299"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Dynamic interaction between tentacle-tethered microdomains in Integrator and NELF regulates the promoter-proximal pause checkpoint [TTchem]","description":"NELF and Integrator are key regulators of promoter-proximal pausing and premature termination. Integrator subunit 12 (INTS12) contains a PHD domain within a flexible linker. While PHDs generally bind histones, we identify an interaction between the INTS12 PHD and a domain in the flexible C-terminal tentacle of NELF-A. Mutation of either domain disrupts the interaction, and although RNAPII-associated pausing complexes form, they are dysfunctional. Importantly, upon NELF-A mutation, interactions of the Integrator-containing pausing complex with transcriptional activators become apparent that correlate with increased pause-escape. Indeed, while INTS12 PHD loss functionally mimics Integrator loss, NELF-A mutation mimics loss of NELF, although the RNAPII pause position does not change. This supports a model in which Integrator is an integral component of the promoter-proximal pausing complex, and where INTS12’s PHD either interacts with NELF-A to pause/terminate transcription or enables interaction with activators and positive transcription regulators to allow pause-escape.","dates":{"publication":"2026/07/08"},"accession":"GSE318299","cross_references":{"GSM":["GSM9491920","GSM9491923","GSM9491924","GSM9491921","GSM9491922","GSM9491927","GSM9491917","GSM9491925","GSM9491926","GSM9491918","GSM9491919"],"GPL":["30173"],"GSE":["318299"],"taxon":["Homo sapiens"]}}