|
| Status |
Public on Oct 07, 2014 |
| Title |
Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming (RNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Reactivation of the pluripotency network during somatic cell reprogramming by exogenous transcription factors involves chromatin remodeling and the recruitment of RNA polymerase II (Pol II) to target loci. Here, we report that Pol II is engaged at pluripotency promoters in reprogramming but remains paused and inefficiently released. We also show that bromodomain-containing protein 4 (BRD4) stimulates productive transcriptional elongation of pluripotency genes by dissociating the pause release factor P-TEFb from an inactive complex containing HEXIM1. Consequently, BRD4 overexpression enhances reprogramming efficiency and HEXIM1 suppresses it, whereas Brd4 and Hexim1 knockdown do the opposite. We further demonstrate that the reprogramming factor KLF4 helps recruit P-TEFb to pluripotency promoters. Our work thus provides a mechanism for explaining the reactivation of pluripotency genes in reprogramming and unveils an unanticipated role for KLF4 in transcriptional pause release.
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| |
|
| Overall design |
Examination of differential gene expression after overexpression of Cdk9-DN at 4 time points of somatic cell reprogramming
|
| |
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| Contributor(s) |
Liu L, Xu Y, He M, Esteban MA |
| Citation(s) |
25312495 |
| |
| Submission date |
Jul 28, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Minghui He |
| E-mail(s) |
hemh@genomics.cn
|
| Organization name |
BGI-Shenzhen
|
| Department |
Cancer Research Department
|
| Street address |
Beishan Industrial Zone, Yantian District
|
| City |
ShenZhen |
| State/province |
GuangDong |
| ZIP/Postal code |
518083 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (14)
|
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| This SubSeries is part of SuperSeries: |
| GSE59833 |
Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming |
|
| Relations |
| BioProject |
PRJNA256307 |
| SRA |
SRP044929 |
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