GEO series
Targeting CDK12/CYCLIN K induces a gene activation program which is mediated by P-TEFb [Cut&RUN]
GSE316989
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
10 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 GSE316989_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 10 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1405630 and SRA study SRP664772. Searching any of these in the dataset finder brings you back here.
Study design
10 conditions, each sampled once — no replicated groups
Read from 10 sample titles: 10 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM9463470 2D10, Untreated, H3K4me3
- GSM9463471 2D10, Untreated, H3K27ac
- GSM9463472 2D10, Untreated, Pol II
- GSM9463473 2D10, Untreated, Ser2-P
- GSM9463474 2D10, Untreated, Ser5-P
- GSM9463475 2D10, Treated, H3K4me3
- GSM9463476 2D10, Treated, H3K27ac
- GSM9463477 2D10, Treated, Pol ll
- GSM9463478 2D10, Treated, Ser2-P
- GSM9463479 2D10, Treated, Ser5-P
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