Publication Date:
2011-08-30
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175327/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175327/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guttman, Mitchell -- Donaghey, Julie -- Carey, Bryce W -- Garber, Manuel -- Grenier, Jennifer K -- Munson, Glen -- Young, Geneva -- Lucas, Anne Bergstrom -- Ach, Robert -- Bruhn, Laurakay -- Yang, Xiaoping -- Amit, Ido -- Meissner, Alexander -- Regev, Aviv -- Rinn, John L -- Root, David E -- Lander, Eric S -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-09/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Aug 28;477(7364):295-300. doi: 10.1038/nature10398.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. mguttman@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21874018" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation/*genetics
;
Cell Lineage/genetics
;
Chromatin/genetics/metabolism
;
Gene Expression Regulation/genetics
;
Gene Knockdown Techniques
;
Mice
;
Pluripotent Stem Cells/*cytology/*metabolism
;
Protein Binding
;
RNA, Untranslated/*genetics/*metabolism
;
Transcription Factors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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