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Series GSE89821 Query DataSets for GSE89821
Status Public on Mar 09, 2017
Title Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis [ChrRNA-seq]
Organism Mus musculus
Experiment type Other
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.
Overall design Chromatin-associated RNA sequencing (ChrRNA-seq) in wild type mESCs with/without JQ1 and DGCR8 knockout mESCs.
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
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)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM2390055 ChrRNA-seq-WT-Control - replicate 1
GSM2390056 ChrRNA-seq-WT-Control - replicate 2
GSM2390057 ChrRNA-seq-WT-JQ1 - replicate 1
This SubSeries is part of SuperSeries:
GSE89826 Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis
BioProject PRJNA353392
SRA SRP093305

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Supplementary file Size Download File type/resource
GSE89821_RAW.tar 2.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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