{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293152/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293152"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Hypoxia-responsive interaction between Cyclin T1, BHLHE40, and Tim8-Tim13 regulates RNA Polymerase II","description":"P-TEFb regulates the pause release checkpoint on transcription by RNA Polymerase II. We sought hypoxia-specific interactions that could direct PTEF-b activity to hypoxia-responsive genes. Using a biochemical purification approach, we discovered a hypoxia-specific, chromatin-associated interaction between the P-TEFb subunit Cyclin T1 (CCNT1), the mitochondrial chaperone Tim8-Tim13 complexes, and the hypoxia-inducible, DNA-binding transcription factor BHLHE40. This interaction is conserved across diverse cell line models. Tim8-Tim13 complex disruption and BHLHE40 silencing both impair the transcriptional response to acute hypoxia by RNAPII in DLD-1 cells. HIF is not involved in the CCNT1/BHLHE40/Tim8-Tim13 interaction, and BHLHE40 expression is not entirely HIF-dependent: neither genetic HIF-1β knockout nor pharmacological inhibition of HIF-2α using belzutifan eliminates BHLHE40. Finally, BHLHE40 depletion compromises the proliferation of 786-O clear cell renal carcinoma cells, which constitutively express HIF-2α and hypoxia-responsive genes. Together, these findings reveal a HIF-independent regulatory axis in which Tim8a-Tim13 complexes and BHLHE40 that modulate PTEF-b activity in the transcriptional response to hypoxia.","dates":{"publication":"2026/04/10"},"accession":"GSE293152","cross_references":{"GSM":["GSM8877502","GSM8877503","GSM8877500","GSM8877489","GSM8877501","GSM8877487","GSM8877488","GSM8877485","GSM8877486","GSM8877508","GSM8877509","GSM8877506","GSM8877507","GSM8877504","GSM8877505","GSM8877483","GSM8877484","GSM8877481","GSM8877482","GSM8877480","GSM8877513","GSM8877514","GSM8877511","GSM8877478","GSM8877512","GSM8877479","GSM8877498","GSM8877476","GSM8877477","GSM8877510","GSM8877499","GSM8877474","GSM8877496","GSM8877497","GSM8877475","GSM8877494","GSM8877472","GSM8877495","GSM8877473","GSM8877492","GSM8877493","GSM8877490","GSM8877491"],"GPL":["30173"],"GSE":["293152"],"taxon":["Homo sapiens"]}}