Scientific Publications

lincRNAs act in the circuitry controlling pluripotency and differentiation.

Publication TypeJournal Article
AuthorsGuttman, M., Donaghey J., Carey BW, Garber M., Grenier JK, Munson G., Young G., Lucas AB, Ach R., Bruhn L., Yang X., Amit I., Meissner A., Regev A., Rinn JL, Root DE, and Lander E. S.
AbstractAlthough 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 Publication2011
JournalNature
Volume477
Issue7364
Pages295-300
Date Published (YYYY/MM/DD)2011/08/28
ISSN Number0028-0836
DOI10.1038/nature10398
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/21874018?dopt=Abstract