|
| Status |
Public on Aug 01, 2017 |
| Title |
Human TFIIH kinase CDK7 regulates transcription-associated epigenetic modification |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
CDK7 phosphorylates the RNA polymerase II (pol II) CTD and activates the P-TEFb- associated kinase, CDK9, but its regulatory roles remain obscure. Using human CDK7 analog-sensitive (CDK7as) cells, we observed reduced capping enzyme recruitment, increased pol II promoter-proximal pausing, and defective termination at gene 3'-ends upon CDK7 inhibition. We also found that CDK7 regulates chromatin modifications downstream of transcription start sites. H3K4me3 spreading was restricted at gene 5'-ends and H3K36me3 was displaced toward gene 3'-ends in CDK7as cells. Together, these results implicate a CDK7-dependent "CTD code" that regulates epigenetic marks in addition to RNA processing and pol II pausing.
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|
| Overall design |
WT and analogue sensitive Cdk7as mutant cells were treated with the ATP analogue NM-PP1 that specifically inhibits the Cdk7as mutant kinase. Using ChIP-seq and RNA-seq we tested the effects of Cdk7 inactivation on pol II distribution along genes, CTD Ser2 and Ser5 phosphorylation, capping enzyme recruitment, histone H3K4 and H3K36 methylation and mRNA expression
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| Contributor(s) |
Bentley D, Erickson B |
| Citation(s) |
28768201 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 GM063873 |
Elongation and termination of transcripts by RNA pol II |
UNIVERSITY OF COLORADO DENVER |
DAVID Leonard BENTLEY |
| R35 GM118051 |
Coupling of transcription with nascent pre-mRNA metabolism |
UNIVERSITY OF COLORADO DENVER |
DAVID Leonard BENTLEY |
|
| Submission date |
Jun 14, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
David L. Bentley |
| E-mail(s) |
david.bentley@ucdenver.edu
|
| Organization name |
U. Colorado School of Medicine
|
| Department |
Biochemistry and Mol. Genetics
|
| Street address |
12801 E. 17th Ave
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (34)
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| Relations |
| BioProject |
PRJNA390543 |
| SRA |
SRP109292 |
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