lincRNAs act in the circuitry controlling pluripotency and differentiation
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Lander_lincRNAs act.pdf
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Author(s)
Guttman, Mitchell
Donaghey, Julie
Carey, Bryce W.
Garber, Manuel
Grenier, Jennifer K.
Munson, Glen
Young, Geneva
Lucas, Anne Bergstom
Ach, Robert
Bruhn, Laurakay
Date Issued
August 2011
Journal
Nature
Publisher
Nature Publishing Group
Citation
Guttman, Mitchell et al. “lincRNAs Act in the Circuitry Controlling Pluripotency and Differentiation.” Nature 477.7364 (2011): 295–300. Web.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nature10398
