lincRNAs act in the circuitry controlling pluripotency and differentiation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-08-28

AUTHORS

Mitchell Guttman, Julie Donaghey, Bryce W. Carey, Manuel Garber, Jennifer K. Grenier, Glen Munson, Geneva Young, Anne Bergstrom Lucas, Robert Ach, Laurakay Bruhn, Xiaoping Yang, Ido Amit, Alexander Meissner, Aviv Regev, John L. Rinn, David E. Root, Eric S. Lander

ABSTRACT

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state. More... »

PAGES

295-300

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature10398

    DOI

    http://dx.doi.org/10.1038/nature10398

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1018204822

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21874018


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