Reference : Analysis of primary microRNA loci from nascent transcriptomes reveals regulatory doma...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
Analysis of primary microRNA loci from nascent transcriptomes reveals regulatory domains governed by chromatin architecture
Bouvy-Liivrand, Maria* [University of Eastern Finland > School of Medicine]
Hernandez de Sande, Ana* [University of Eastern Finland]
Pölönen, Petri [University of Eastern Finland]
Mehtonen, Juha [University of Eastern Finland]
Vuorenmaa, Tapio [University of Eastern Finland]
Niskanen, Henri [University of Eastern Finland > A. I. Virtanen Institute]
Sinkkonen, Lasse mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Kaikkonen, Minna [University of Eastern Finland > A. I. Virtanen Institute]
Heinäniemi, Merja [University of Eastern Finland > School of Medicine]
* These authors have contributed equally to this work.
Nucleic Acids Research
Oxford University Press
Yes (verified by ORBilu)
United Kingdom
[en] Changes in mature microRNA (miRNA) levels that occur downstream of signaling cascades play an important role during human development and disease. However, the regulation of primary microRNA (pri-miRNA) genes remains to be dissected in detail. To address this, we followed a data-driven approach and developed a transcript identification, validation and quantification pipeline for characterizing the regulatory domains of pri-miRNAs. Integration of 92 nascent transcriptomes and multilevel data from cells arising from ecto-, endo- and mesoderm lineages reveals cell type-specific expression patterns, allows fine-resolution mapping of transcription start sites (TSS) and identification of candidate regulatory regions. We show that inter- and intragenic pri-miRNA transcripts span vast genomic regions and active TSS locations differ across cell types, exemplified by the mir-29a∼29b-1, mir-100∼let-7a-2∼125b-1 and miR-221∼222 clusters. Considering the presence of multiple TSS as an important regulatory feature at miRNA loci, we developed a strategy to quantify differential TSS usage. We demonstrate that the TSS activities associate with cell type-specific super-enhancers, differential stimulus responsiveness and higher-order chromatin structure. These results pave the way for building detailed regulatory maps of miRNA loci.
Fondation du Pélican de Marie et Pierre Hippert-Faber

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