Elucidating microRNA regulatory networks using transcriptional, post-transcriptional and histone modification measurements
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Sara Gosline
PROVIDER: E-GEOD-61035 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:RNA-Seq performed on Dicer KO and WT murine mesenchymal stem cells MicroRNAs (miRNAs) are small non-coding RNAs that regulates development and disease but induce only moderate repression of directs mRNA targets, suggesting that they coordinate with other modes ofs cellular regulation to effect large changes in gene expression. Ins this work we decouple direct effects of global miRNA loss froms transcriptional changes downstream in a pair of isogenic murines fibroblast cell lines with and without Dicer expression. Wes demonstrate how effects on direct miRNA targets are amplified bys transcription machinery through the construction of a network models that identifies specific transcription factors that cause changes ins mRNA expression upon Dicer loss. Through transcription factors over-expression, we delineate miRNA-mediated transcriptional programss and identify miRNA-mediated coherent and incoherent feed-forwards loops, suggesting a functional role of the interaction between miRNAss and transcription factors. In total, our results indicate thats miRNAs tightly control transcription factors within a denses interconnected network to modulate gene expression. Examination of mature mRNA expression changes in adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-).
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