ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation

Sharma Nikhil; Pollina Elizabeth A.; Nagy M. Aurel; Yap Ee-Lynn; DiBiase Florence A.; Hrvatin Sinisa; Hu Linda; Lin Cindy; Greenberg Michael E.

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ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation

机译：ARNT2通过Ncor2介导的抑制和NPAS4介导的活化调节活性依赖性基因表达

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Neuronal activity-dependent transcription is tuned to ensure precise gene induction during periods of heightened synaptic activity, allowing for appropriate responses of activated neurons within neural circuits. The consequences of aberrant induction of activity-dependent genes on neuronal physiology are not yet clear. Here, we demonstrate that, in the absence of synaptic excitation, the basic-helixloop-helix (bHLH)-PAS family transcription factor ARNT2 recruits the NCoR2 co-repressor complex to suppress neuronal activity-dependent regulatory elements and maintain low basal levels of inducible genes. This restricts inhibition of excitatory neurons, maintaining them in a state that is receptive to future sensory stimuli. By contrast, in response to heightened neuronal activity, ARNT2 recruits the neuronal-specific bHLH-PAS factor NPAS4 to activity-dependent regulatory elements to induce transcription and thereby increase somatic inhibitory input. Thus, the interplay of bHLH-PAS complexes at activity-dependent regulatory elements maintains temporal control of activity-dependent gene expression and scales somatic inhibition with circuit activity.

机译：调整神经元活性依赖性转录以确保在突触活动的时期期间确保精确的基因诱导，从而允许在神经电路内的活性神经元进行适当的反应。异常诱导活性依赖性基因对神经元生理的后果尚不清楚。在这里，我们证明，在没有突触激发的情况下，基本 - 螺旋螺旋（BHLH）-PAS系列转录因子ARNT2促进Ncor2副压制络合物以抑制神经元活性依赖性调节元件，并保持低基础水平的诱导基因。这限制了对兴奋性神经元的抑制作用，以容纳未来感官刺激的状态维持它们。相比之下，响应于神经元活性的高度，ARNT2将神经元特异性的BHLH-PAS因子NPAS4递给活性依赖性调节元件，以诱导转录，从而增加体细胞抑制剂。因此，在活性依赖性调节元件下的BHLH-PAS络合物的相互作用维持活性依赖性基因表达的时间控制，并用电路活性缩放体细胞抑制。

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《Neuron》 |2019年第2期|共26页
作者
Sharma Nikhil; Pollina Elizabeth A.; Nagy M. Aurel; Yap Ee-Lynn; DiBiase Florence A.; Hrvatin Sinisa; Hu Linda; Lin Cindy; Greenberg Michael E.;
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Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

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正文语种 eng
中图分类神经病学;
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1. ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation [J] . Sharma Nikhil, Pollina Elizabeth A., Nagy M. Aurel, Neuron . 2019,第2期

机译：ARNT2通过Ncor2介导的抑制和NPAS4介导的活化调节活性依赖性基因表达
2. Design and characterization of a dual-mode promoter with activation and repression capability for tuning gene expression in yeast [J] . Mazumder Mostafizur, McMillen David R. Nucleic Acids Research . 2014,第14期

机译：具有激活和抑制功能的双模式启动子的设计和表征，用于调节酵母中的基因表达
3. PRC1 fine-tunes gene repression and activation to safeguard skin epithelium development and stem cell specification [J] . Cohen I., Zhao D., Zheng D., The Journal of investigative dermatology. . 2018,第5a19期

机译：PRC1微调基因抑制和活化，以保护皮肤上皮开发和干细胞规格
4. Reciprocal expressions of VEGF and the numbers of dendritic cells in arsenic-induced skin cancer: A plausible cause of impaired dendritic cell activation in arsenic carcinogenesis [C] . C.-H. Lee, C.-H. Hong, H.-S. Yu International Congress on Arsenic in the Environment . 2016

机译：VEGF的互惠表达和砷诱导的皮肤癌中的树突细胞数：砷致癌中的树突细胞活性受损的可粘性原因
5. Activation and repression of activity -dependent expression of brain-derived neurotrophic factor (BDNF). [D] . Chen, Wen Grace. 2003

机译：脑源性神经营养因子（BDNF）的活性依赖性表达的激活和抑制。
6. Design and characterization of a dual-mode promoter with activation and repression capability for tuning gene expression in yeast [O] . Mostafizur Mazumder, David R. McMillen 2014

机译：具有激活和抑制功能的双模式启动子的设计和表征用于调节酵母中的基因表达
7. ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation [O] . Nikhil Sharma, Elizabeth A. Pollina, M. Aurel Nagy, 2019

机译：ARNT2通过Ncor2介导的抑制和NPAS4介导的活化调节活性依赖性基因表达

ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation

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