Abstract
Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division.
Original language | English (US) |
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Pages (from-to) | 435-445 |
Number of pages | 11 |
Journal | Molecular cell |
Volume | 60 |
Issue number | 3 |
DOIs | |
State | Published - Nov 5 2015 |
Funding
We thank the Molecular Biology core facility at the Stowers Institute for creating and sequencing libraries for next-generation sequencing and the Tissue Culture facility for large-scale cell culture. We thank Dr. Edwin Smith for helpful discussions, and Laura Shilatifard for editorial assistance. This work was performed to fulfill, in part, requirements for the PhD thesis research of K.L. as a student registered with the Open University. This study was supported by grant R01GM069905 from the NIH (to A.H.).
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology