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Status |
Public on Mar 19, 2024 |
Title |
Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9 (TS11dTAG_NVP2_POINT-seq) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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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.
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Overall design |
Comparative gene expression and meta analysis of chromatin RNA by polymerase intact nascent transcript (POINT-Seq) for HCT116 INTS-dTAG degron (with or without dTAG and with or without NVP2)
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Contributor(s) |
Eaton JD, Board J, Davidson L, Estell C, West S |
Citation(s) |
38976490 |
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Submission date |
Sep 14, 2023 |
Last update date |
Aug 08, 2024 |
Contact name |
Steven West |
E-mail(s) |
s.west@exeter.ac.uk
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Phone |
0044(0)1392727458
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Organization name |
University of Exeter
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Department |
Living Systems Institute
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Street address |
Stocker Rd
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City |
Exeter |
State/province |
Devon |
ZIP/Postal code |
EX4 4QD |
Country |
United Kingdom |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (10)
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GSM7782462 |
Rep1 POINT-Seq NVP2 INTS11 minus dTAGv-1 |
GSM7782463 |
Rep1 POINT-Seq NVP2 INTS11 plus dTAGv-1 |
GSM7782464 |
Rep1 POINT-Seq NVP2 INTS11 plus NVP2 |
GSM7782465 |
Rep1 POINT-Seq NVP2 INTS11 plus dTAGv-3 and plus NVP2 |
GSM7782466 |
Rep2 POINT-Seq NVP2 INTS11 minus dTAGv-1 |
GSM7782467 |
Rep2 POINT-Seq NVP2 INTS11 plus dTAGv-1 |
GSM7782468 |
Rep2 POINT-Seq NVP2 INTS11 plus NVP2 |
GSM7782469 |
Rep2 POINT-Seq NVP2 INTS11 plus dTAGv-3 and plus NVP2 |
GSM7782470 |
Rep3 POINT-Seq NVP2 INTS11 plus NVP2 |
GSM7782471 |
Rep3 POINT-Seq NVP2 INTS11 plus dTAGv-3 and plus NVP2 |
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This SubSeries is part of SuperSeries: |
GSE243266 |
Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9 |
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Relations |
BioProject |
PRJNA1017499 |