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| Status |
Public on Mar 09, 2017 |
| Title |
Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis [X-ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Super-enhancers are an emerging sub-class of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA processing. Super-enhancers, together with broad H3K4me3 domains, shape a tissue-specific and evolutionarily conserved atlas of miRNA expression and function. CRISPR/Cas9 genomics revealed that super-enhancer constituents act cooperatively and facilitate Drosha/DGCR8 recruitment and pri-miRNA processing to boost cell-specific miRNA production. BET-bromodomain inhibitor JQ1 preferentially inhibited super-enhancer-directed cotranscriptional pri-miRNA processing. Furthermore, super-enhancers are characterized by pervasive interaction with DGCR8/Drosha and DGCR8/Drosha-regulated mRNA stability control, suggesting unique RNA regulation at super-enhancers. Finally, super-enhancers mark multiple miRNAs associated with cancer hallmark traits. This study presents a principle underlying miRNA biology in health and disease and a unrecognized higher-order property of super-enhancers in RNA processing beyond transcription.
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| |
|
| Overall design |
X-ChIP-seq of DGCR8 and Drosha in mESCs with/without JQ1.
|
| |
|
| Contributor(s) |
Suzuki HI, Young RA, Sharp PA |
| Citation(s) |
28283057 |
| Submission date |
Nov 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Hiroshi I. Suzuki |
| E-mail(s) |
hisuzuki-tky@umin.ac.jp
|
| Organization name |
Nagoya University
|
| Department |
DIvision of Molecular Oncology, Graduate School of Medicine
|
| Street address |
65 Tsurumai-cho, Showa-ku
|
| City |
Nagoya |
| ZIP/Postal code |
466-8550 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (5)
|
|
| This SubSeries is part of SuperSeries: |
| GSE89826 |
Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis |
|
| Relations |
| BioProject |
PRJNA353390 |
| SRA |
SRP093303 |
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