GEO series
Targeting CDK12/CYCLIN K induces a gene activation program which is mediated by P-TEFb
GSE316689
Homo sapiens
Expression profiling by high throughput sequencing
8 samples
Submitted 2026/08/07
Platform GPL30173
Summary
Regulation of transcription in human cells is a multistep process controlled by coordinated actions of host transcription factors and their associated kinases. Despite major advances, fundamental gaps still remain in understanding how transcriptional programs are dynamically regulated. Gene expression of Human immunodeficiency virus (HIV) is tightly controlled by the cellular transcription machinery, providing a powerful model for studying transcription regulation. Such gene expression regulation is clinically significant, as HIV persists in long-lived reservoirs even under antiretroviral therapy. Here, we show that selective targeting of CDK12/CYCLIN K (CCNK) induces a global gene activation program, which is mediated by positive transcription elongation factor b (P-TEFb). CDK12/CCNK targeting reshapes promoter-proximal and gene bodies landscape at chromatin, and promotes release of P-TEFb from its inhibitory 7SK snRNP complex. Additional transcriptomic profiling reveals preferential upregulation of P-TEFb-target genes, accompanied by induction of relatively short genes and repression of CDK12-regulated DNA damage response pathways. In HIV- infected cells, targeting CDK12/CCNK activates a robust viral gene expression, accompanied with latency reversal and importantly, synergistic reactivation effects when combined with latency- reversing agents. Together, these results uncover a previously unrecognized compensatory interplay between transcriptional kinases that rewires the cellular gene expression program with implications for HIV latency reversal and cancer biology.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE316689_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1403602 and SRA study SRP662880. Searching any of these in the dataset finder brings you back here.
Study design
8 conditions, each sampled once — no replicated groups
Read from 8 sample titles: 8 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9458362 Sample 1 Untreated
- GSM9458363 Sample 2 Untreated
- GSM9458364 Sample 3 Untreated
- GSM9458365 Sample 4 Untreated
- GSM9458366 Sample 1 Treated
- GSM9458367 Sample 2 Treated
- GSM9458368 Sample 3 Treated
- GSM9458369 Sample 4 Treated
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