The Tissue-Specific lncRNA Fendrr Is an Essential Regulator of Heart and Body Wall Development in the Mouse
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Kellis_The tissue-specific.pdf
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Author(s)
Grote, Phillip
Wittler, Lars
Hendrix, David A.
Koch, Frederic
Beisaw, Arica
Macura, Karol
Kellis, Manolis
Werber, Martin
Herrmann, Bernhard G.
Wahrisch, Sandra
Date Issued
January 2013
Journal
Developmental Cell
Publisher
Elsevier
Citation
Grote, Phillip, Lars Wittler, David Hendrix, Frederic Koch, Sandra Wahrisch, Arica Beisaw, Karol Macura, et al. “The Tissue-Specific lncRNA Fendrr Is an Essential Regulator of Heart and Body Wall Development in the Mouse.” Developmental Cell 24, no. 2 (January 2013): 206–214. © 2013 Elsevier Inc.
Version
Final published version
Abstract
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 (lncRNAs) 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 lncRNA 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 lncRNA that plays an essential role in the regulatory networks controlling the fate of lateral mesoderm derivatives.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2012.12.012
