The Tissue-Specific IncRNA Fendrr Is an Essential Regulator of Heart and Body Wall Development in the Mouse

被引：776

作者：

Grote, Phillip ^{[1
]}

Wittler, Lars ^{[1
]}

Hendrix, David ^{[3
,4
]}

Koch, Frederic ^{[1
]}

Waehrisch, Sandra ^{[1
]}

Beisaw, Arica ^{[1
]}

Macura, Karol ^{[1
]}

Blaess, Gaby ^{[1
]}

Kellis, Manolis ^{[3
,4
]}

Werber, Martin ^{[1
]}

Herrmann, Bernhard G. ^{[1
,2
]}

机构：

[1] Max Planck Inst Mol Genet, Dept Dev Genet, D-14195 Berlin, Germany

[2] Charite, Inst Med Genet, D-12203 Berlin, Germany

[3] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[4] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA

来源：

DEVELOPMENTAL CELL | 2013年 / 24卷 / 02期

基金：

美国国家科学基金会;

关键词：

LONG NONCODING RNA; GENE-EXPRESSION; POLYCOMB; CHROMATIN; PROTEINS; DIFFERENTIATION; MESODERM; MORPHOGENESIS; DISSECTION; COMPLEXES;

D O I：

10.1016/j.devcel.2012.12.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The histone-modifying complexes PRC2 and TrxG/MLL play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long noncoding RNAs (IncRNAs) can bind to either complex, and some have been shown to act as modulators of PRC2 or TrxG/MLL activity. Here we show that the lateral mesoderm-specific IncRNA Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in PRC2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the PRC2 and TrxG/MLL complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, we identified an IncRNA that plays an essential role in the regulatory networks controlling the fate of lateral mesoderm derivatives.

引用

页码：206 / 214

页数：9

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