GEO series
Hypoxia-responsive interaction between Cyclin T1, BHLHE40, and Tim8-Tim13 regulates RNA Polymerase II
GSE293152
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
43 samples
Submitted 2026/04/10
Platform GPL30173
Summary
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.
Published in
Soliman SHA, De Fabritiis S, Iwanaszko M et al.
· Science advances 2026
· PMID 42160428
· doi:10.1126/sciadv.adz9295
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE293152_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 43 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1242900 and SRA study SRP573700. Searching any of these in the dataset finder brings you back here.
Study design
40 conditions, each sampled once — no replicated groups
Read from the first 40 of 43 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8877472 ChIP_01_pSer2_gRNActrl_Normoxia.RPKM
- GSM8877473 ChIP_02_pSer2_gRNActrl_Hypoxia.RPKM
- GSM8877474 ChIP_03_pSer2_TIMM13.TIMM8A_KO1_Hypoxia.RPKM
- GSM8877475 ChIP_04_pSer2_TIMM13.TIMM8A_KO2_Hypoxia.RPKM
- GSM8877476 ChIP_05_pSer2_TIMM13.TIMM8B_KO1_Hypoxia.RPKM
- GSM8877477 ChIP_06_pSer2_TIMM13.TIMM8B_KO2_Hypoxia.RPKM
- GSM8877478 ChIP_07_pSer2_Input.Rx
- GSM8877479 ChIP_08_Pol2_gRNActrl_Normoxia
- GSM8877480 ChIP_09_Pol2_gRNActrl_Hypoxia
- GSM8877481 ChIP_10_Pol2_TIMM13.TIMM8A_KO1_Hypoxia
- GSM8877482 ChIP_11_Pol2_TIMM13.TIMM8A_KO2_Hypoxia
- GSM8877483 ChIP_12_Pol2_TIMM13.TIMM8B_KO1_Hypoxia
- GSM8877484 ChIP_13_Pol2_TIMM13.TIMM8B_KO2_Hypoxia
- GSM8877485 ChIP_14_Pol2_HIF1B_KO_Hypoxia
- GSM8877486 ChIP_15_Pol2_Input
- GSM8877487 ChIP_16_Pol2_gRNActrl_Normoxia
- GSM8877488 ChIP_17_Pol2_gRNActrl_Hypoxia
- GSM8877489 ChIP_18_Pol2_TIMM8A_KO1_Hypoxia
- GSM8877490 ChIP_19_Pol2_TIMM8A_KO2_Hypoxia
- GSM8877491 ChIP_20_Pol2_TIMM8B_KO1_Hypoxia
- GSM8877492 ChIP_21_Pol2_TIMM8B_KO2_Hypoxia
- GSM8877493 ChIP_22_Pol2_TIMM13_KO1_Hypoxia
- GSM8877494 ChIP_23_Pol2_TIMM13_KO2_Hypoxia
- GSM8877495 ChIP_24_Pol2_TIMM13.TIMM8A_KO1_Normoxia
- GSM8877496 ChIP_25_Pol2_TIMM13.TIMM8A_KO2_Normoxia
- GSM8877497 ChIP_26_Pol2_TIMM13.TIMM8B_KO1_Normoxia
- GSM8877498 ChIP_28_Pol2_INPUT
- GSM8877499 ChIP_29_Pol2_shctrl_Normoxia
- GSM8877500 ChIP_30_Pol2_shBHLHE40_Normoxia
- GSM8877501 ChIP_31_Pol2_shctrl_Hypoxia
- GSM8877502 ChIP_32_Pol2_shBHLHE40_Hypoxia
- GSM8877503 ChIP_34_BHLHE40_shctrl_Normoxia.Rx
- GSM8877504 ChIP_35_BHLHE40_shctrl_Hypoxia.Rx
- GSM8877505 ChIP_36_BHLHE40_shBHLHE40_Hypoxia.Rx
- GSM8877506 ChIP_37_BHLHE40_Input.Rx
- GSM8877507 ChIP_38_BHLHE40_gRNActrl_Normoxia.Rx
- GSM8877508 ChIP_39_BHLHE40_gRNActrl_Hypoxia.Rx
- GSM8877509 ChIP_40_BHLHE40_HIF1B.KO1_Hypoxia.Rx
- GSM8877510 ChIP_41_BHLHE40_BHLHE40.KO1_Hypoxia.Rx
- GSM8877511 ChIP_42_HIF1A_gRNActrl_Normoxia.Rx
+ 3 more — browse all 43 samples with per-sample file links →
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