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Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways

Gruber, Andreas J. and Grandy, William A. and Balwierz, Piotr J. and Dimitrova, Yoana A. and Pachkov, Mikhail and Ciaudo, Constance and van Nimwegen, Erik and Zavolan, Mihaela. (2014) Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways. Nucleic acids research, Vol. 42, H. 14. S. 9313-9326.

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Official URL: http://edoc.unibas.ch/dok/A6298836

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Abstract

The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Gruber, Andreas J. and Grandy, William Aaron and Balwierz, Piotr PJ and Dimitrova, Yoana Aleksandrova and Pachkov, Mikhail and van Nimwegen, Erik
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0305-1048
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:29
Deposited On:07 Nov 2014 08:29

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