CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes
Transcription through early-elongation checkpoints requires phosphorylation of negative transcription elongation factors (NTEFs) by the cyclin-dependent kinase (CDK)9. Using CDK9 inhibitors and global run-on sequencing (GRO-seq), we have mapped CDK9 inhibitor-sensitive checkpoints genome-wide in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Nature Publishing Group
2015
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/1/2015-NSMB.pdf http://irep.iium.edu.my/60432/7/60432_CDK9%20inhibitors%20define%20elongation_scopus.pdf |
| Summary: | Transcription through early-elongation checkpoints requires phosphorylation of negative
transcription elongation factors (NTEFs) by the cyclin-dependent kinase (CDK)9. Using CDK9
inhibitors and global run-on sequencing (GRO-seq), we have mapped CDK9 inhibitor-sensitive
checkpoints genome-wide in human (Homo sapiens) cells. Our data indicate that early-elongation
checkpoints are a general feature of RNA polymerase (pol) II-transcribed human genes and occur
independently of polymerase stalling. Pol II that has negotiated the early-elongation checkpoint
can elongate in the presence of inhibitors but, remarkably, terminates transcription prematurely
close to the terminal polyadenylation (poly(A)) site. Our analysis has revealed a hithertounsuspected
poly(A)-associated elongation checkpoint, which has major implications for the
regulation of gene expression. Interestingly, the pattern of modification of the carboxyl-terminal
domain (CTD) of pol II terminated at this novel checkpoint largely mirrors the pattern normally
found downstream of the poly(A) site, suggesting common mechanisms of termination |
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