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Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9 (INTS11-dTAG_ChIP-seq)

GSE243259 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/03/19 Platform GPL24676
Summary
RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
Published in
Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9
Eaton JD, Board J, Davidson L et al. · eLife 2024 · PMID 38976490 · doi:10.7554/eLife.92764
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Also filed as BioProject PRJNA1017496 and SRA study SRP460599. Searching any of these in the dataset finder brings you back here.

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