lincRNAs act in the circuitry controlling pluripotency and differentiation

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 and Eric S. Lander ()
Additional contact information
Mitchell Guttman: Broad Institute of MIT and Harvard, 7 Cambridge Center
Julie Donaghey: Broad Institute of MIT and Harvard, 7 Cambridge Center
Bryce W. Carey: Massachusetts Institute of Technology
Manuel Garber: Broad Institute of MIT and Harvard, 7 Cambridge Center
Jennifer K. Grenier: Broad Institute of MIT and Harvard, 7 Cambridge Center
Glen Munson: Broad Institute of MIT and Harvard, 7 Cambridge Center
Geneva Young: Broad Institute of MIT and Harvard, 7 Cambridge Center
Anne Bergstrom Lucas: Genomics Research and Development, Agilent Technologies
Robert Ach: Genomics Research and Development, Agilent Technologies
Laurakay Bruhn: Genomics Research and Development, Agilent Technologies
Xiaoping Yang: Broad Institute of MIT and Harvard, 7 Cambridge Center
Ido Amit: Broad Institute of MIT and Harvard, 7 Cambridge Center
Alexander Meissner: Broad Institute of MIT and Harvard, 7 Cambridge Center
Aviv Regev: Broad Institute of MIT and Harvard, 7 Cambridge Center
John L. Rinn: Broad Institute of MIT and Harvard, 7 Cambridge Center
David E. Root: Broad Institute of MIT and Harvard, 7 Cambridge Center
Eric S. Lander: Broad Institute of MIT and Harvard, 7 Cambridge Center

Nature, 2011, vol. 477, issue 7364, 295-300

Abstract: 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.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature10398 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:477:y:2011:i:7364:d:10.1038_nature10398

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature10398

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().