Widespread transcription at neuronal activity-regulated enhancers.
Widespread transcription at neuronal activity-regulated enhancers.
复制标题
作者：
我们使用全基因组测序方法来研究神经元中的刺激依赖性增强子功能。我们确定了12,000个神经元活性调节增强子，它们以活性依赖性方式与一般转录辅激活因子CBP结合。CBP在增强子处的功能可能是募集RNA聚合酶II（RNAPII），因为我们还观察到活性调节的RNAPII与数千个增强子结合。值得注意的是，RNAPII在增强子处双向转录增强子结构域内的一类新的增强子RNA（eRNA），所述增强子结构域由在赖氨酸4处单甲基化的组蛋白H3（H3 K4 me 1）的存在限定。神经元增强子的eRNA表达水平与附近基因的mRNA合成水平呈正相关，表明eRNA合成特异性地发生在积极参与促进mRNA合成的增强子处。这些发现揭示了增强子激活的广泛机制涉及RNAPII结合和eRNA合成。
We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. We identified ∼12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Remarkably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 that is mono-methylated at lysine 4 (H3K4me1). The level of eRNA expression at neuronal enhancers positively correlates with the level of mRNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.
登录
查看更多内容
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
16.2
作者：
Plath, Niels;Ohana, Ora;Kuhl, Dietmar
通讯作者：
Kuhl, Dietmar