GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293152/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293152GEOGSEfalseHypoxia-responsive interaction between Cyclin T1, BHLHE40, and Tim8-Tim13 regulates RNA Polymerase IIP-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.2026/04/10GSE293152GSM8877502GSM8877503GSM8877500GSM8877489GSM8877501GSM8877487GSM8877488GSM8877485GSM8877486GSM8877508GSM8877509GSM8877506GSM8877507GSM8877504GSM8877505GSM8877483GSM8877484GSM8877481GSM8877482GSM8877480GSM8877513GSM8877514GSM8877511GSM8877478GSM8877512GSM8877479GSM8877498GSM8877476GSM8877477GSM8877510GSM8877499GSM8877474GSM8877496GSM8877497GSM8877475GSM8877494GSM8877472GSM8877495GSM8877473GSM8877492GSM8877493GSM8877490GSM887749130173293152Homo sapiens