The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse.
The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse.
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DOI：
10.1016/j.devcel.2012.12.012
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发表时间：
2013-01-28
影响因子：
11.8
通讯作者：
Herrmann, Bernhard G.
中科院分区：
文献类型：
--
作者：
Grote, Phillip;Wittler, Lars;Hendrix, David;Koch, Frederic;Waehrisch, Sandra;Beisaw, Arica;Macura, Karol;Blaess, Gaby;Kellis, Manolis;Werber, Martin;Herrmann, Bernhard G.
组蛋白修饰复合物PRC 2和TrxG/MLL在决定控制多能性、谱系定型和细胞分化的基因的活化状态中起关键作用。长链非编码RNA（lncRNA）可以与任一复合物结合，并且一些已显示出作为PRC 2或TrxG/MLL活性的调节剂。在这里，我们表明，侧中胚层特异性lncRNA Fendrr是必不可少的适当的心脏和体壁发育的小鼠。缺乏Fendrr的胚胎显示控制侧板或心脏中胚层分化的几种转录因子的上调，伴随着PRC 2占据率的急剧减少，沿着在其启动子处H3 K27三甲基化降低和/或H3 K4三甲基化增加。Fendrr结合PRC 2和TrxG/MLL复合物，表明它作为定义基因活性的染色质特征的调节剂。因此，我们的工作确定了一个lncRNA，发挥了重要的作用，在微调的调控网络，控制的命运侧中胚层衍生物。
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 non-coding 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, our work identifies a lncRNA that plays an essential role in fine-tuning the regulatory networks which control the fate of lateral mesoderm derivatives.
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影响因子：
2.6
作者：
Peterson, RS;Lim, L;Costa, RH
通讯作者：
Costa, RH
影响因子：
64.8
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影响因子：
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作者：
Buske FA;Bauer DC;Mattick JS;Bailey TL
通讯作者：
Bailey TL
影响因子：
14.9
作者：
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通讯作者：
Lawrence, CE
影响因子：
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作者：
O'Carroll, D;Erhardt, S;Jenuwein, T
通讯作者：
Jenuwein, T