A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element.
A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element.
复制标题
DOI：
10.1038/ng.3058
复制
发表时间：
2014-09
期刊：
影响因子：
30.8
通讯作者：
Ringrose, Leonie
中科院分区：
文献类型：
--
作者：
Herzog, Veronika A.;Lempradl, Adelheid;Trupke, Johanna;Okulski, Helena;Altmutter, Christina;Ruge, Frank;Boidol, Bernd;Kubicek, Stefan;Schmauss, Gerald;Aumayr, Karin;Ruf, Marius;Pospisilik, Andrew;Dimond, Andrew;Senergin, Hasene Basak;Vargas, Marcus L.;Simon, Jeffrey A.;Ringrose, Leonie
Polycomb/Trithorax 响应元件（PRE/TRE）可以通过我们知之甚少的机制在沉默和激活之间可逆地切换其功能。在这里，我们展示了果蝇退化 (vg) PRE/TRE 的正向和反向非编码转录的转换，在沉默（由正向链诱导）和激活（由反向链诱导）之间切换元件的状态。在体外，两种 ncRNA 均抑制 PRC2 组蛋白甲基转移酶活性，但在体内只有反向链结合 PRC2。反向链的过度表达会将 PRC2 从染色质中逐出并抑制其酶活性。我们提出，RNA 与 PRC2 的相互作用在体内受到差异性调节，从而可以调节局部 PRC2 活性的抑制。全基因组分析表明，ncRNA 的链转换发生在果蝇和脊椎动物基因组中的数百个 PcG 结合位点。这项工作确定了一类新颖且可能广泛传播的 PRE/TRE，它们通过切换 ncRNA 转录方向来切换功能。
Polycomb/Trithorax response elements (PRE/TREs) can switch their function reversibly between silencing and activation, by mechanisms that are poorly understood. Here we show that a switch in forward and reverse noncoding transcription from the Drosophila vestigial (vg) PRE/TRE switches the status of the element between silencing (induced by the forward strand) and activation (induced by the reverse strand). In vitro, both ncRNAs inhibit PRC2 histone methyltransferase activity, but in vivo only the reverse strand binds PRC2. Over-expression of the reverse strand evicts PRC2 from chromatin and inhibits its enzymatic activity. We propose that interactions of RNAs with PRC2 are differentially regulated in vivo, allowing regulated inhibition of local PRC2 activity. Genome-wide analysis shows that strand switching of ncRNAs occurs at several hundred PcG binding sites in fly and vertebrate genomes. This work identifies a novel and potentially widespread class of PRE/TREs that switch function by switching the direction of ncRNA transcription.
登录
查看更多内容
影响因子：
16.8
作者：
Kaneko, Syuzo;Son, Jinsook;Shen, Steven S.;Reinberg, Danny;Bonasio, Roberto
通讯作者：
Bonasio, Roberto
影响因子：
16
作者：
Cifuentes-Rojas, Catherine;Hernandez, Alfredo J.;Sarma, Kavitha;Lee, Jeannie T.
通讯作者：
Lee, Jeannie T.
影响因子：
16
作者：
Kanhere A;Viiri K;Araújo CC;Rasaiyaah J;Bouwman RD;Whyte WA;Pereira CF;Brookes E;Walker K;Bell GW;Pombo A;Fisher AG;Young RA;Jenner RG
通讯作者：
Jenner RG
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.