Myc-regulated microRNAs attenuate embryonic stem cell differentiation. Export

@article{citeulike:5774747, abstract = {Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation.}, author = {Lin, Chin-Hsing H. and Jackson, Aimee L. and Guo, Jie and Linsley, Peter S. and Eisenman, Robert N.}, citeulike-article-id = {5774747}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2009.254}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/emboj2009254a}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19745813}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19745813}, day = {21}, doi = {10.1038/emboj.2009.254}, issn = {1460-2075}, journal = {The EMBO journal}, keywords = {chip, mirna, myc, qpcr, target\_genes}, month = {October}, number = {20}, pages = {3157--3170}, posted-at = {2009-10-28 18:02:16}, priority = {2}, publisher = {Nature Publishing Group}, title = {Myc-regulated microRNAs attenuate embryonic stem cell differentiation.}, url = {http://dx.doi.org/10.1038/emboj.2009.254}, volume = {28}, year = {2009} }

TY - JOUR ID - citeulike:5774747 L3 - citeulike-article-id:5774747 N2 - Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation. IS - 20 JF - The EMBO journal SN - 1460-2075 EP - 3170 TI - Myc-regulated microRNAs attenuate embryonic stem cell differentiation. PB - Nature Publishing Group VL - 28 SP - 3157 KW - chip KW - mirna KW - myc KW - qpcr KW - target_genes AU - Lin, Chin-Hsing AU - Jackson, Aimee AU - Guo, Jie AU - Linsley, Peter AU - Eisenman, Robert PY - 2009/10/21/ UR - http://dx.doi.org/10.1038/emboj.2009.254 ER -