lincRNAs act in the circuitry controlling pluripotency and differentiation.

Nature
Authors
Keywords
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.

Year of Publication
2011
Journal
Nature
Volume
477
Issue
7364
Pages
295-300
Date Published
2011 Aug 28
ISSN
1476-4687
DOI
10.1038/nature10398
PubMed ID
21874018
PubMed Central ID
PMC3175327
Links
Grant list
U54 HG003067 / HG / NHGRI NIH HHS / United States
U54 HG003067-09 / HG / NHGRI NIH HHS / United States