Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published September 15, 2011 | Supplemental Material + Accepted Version
Journal Article Open

lincRNAs act in the circuitry controlling pluripotency and differentiation

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.

Additional Information

© 2011 Macmillan Publishers Limited. Received 28 March 2011; Accepted 26 July 2011; Published online 28 August 2011. We thank D. Rivera, T. Green, T. Bhimdi, G. Verstappen, C. Surka, S. Silver, A. Brown, D. Lam and O. Ram for technical help; C. Gifford, S. Markoulaki and R. Jaenisch for providing cell lines used in this study; P. Tsang, B. Curry, A. Tsalenko and Agilent Technologies for microarray and technical help; B. Challis and Active Motif for antibodies; G. Geiss, R. Boykin and Nanostring technologies for technical help; E. Wang and C. Burge for help with RNA immunoprecipitation experiments and helpful discussions; P. Gupta, A. Gnirke, J. Cassady, E. Lieberman-Aiden, M. Cabili and M. Thompson for discussions and ideas; and L. Gaffney for assistance with figures. M. Guttman is a Vertex scholar. This work was funded by NHGRI, a Center for Excellence for Genomic Science, the Merkin Foundation for Stem Cell Research, and funds from the Broad Institute of MIT and Harvard.

Attached Files

Accepted Version - nihms314381.pdf

Supplemental Material - nature10398-s1.pdf

Supplemental Material - nature10398-s2.zip

Files

nihms314381.pdf
Files (11.9 MB)
Name Size Download all
md5:6231039c84c9398af92aa6c057ef0f84
1.7 MB Preview Download
md5:cfd4aa853ee2f37962f7babdc5e64397
6.0 MB Preview Download
md5:477ee1c727ab5f16adf40535751033fd
4.1 MB Preview Download

Additional details

Created:
August 19, 2023
Modified:
October 23, 2023