lincRNAs act in the circuitry controlling pluripotency and differentiation
biocq 添加于 2012-3-25 14:07
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作 者
Guttman 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, Lander ES 摘 要
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.-
详细资料
- 关键词: 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
- 文献种类: Journal Article
- 期刊名称: Nature
- 期刊缩写: Nature
- 期卷页: 2011年 第477卷 第7364期 295-300页
- 地址: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. mguttman@mit.edu
- ISBN: 0028-0836
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学科领域 生物医药 » 生物学
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