Epigenetic gene regulation shapes neuronal fate in the embryonic nervous system. Post-embryonically, epigenetic signaling within neurons has been associated with impaired learning, autism, ataxia, and schizophrenia. Epigenetic factors are also enriched in glial cells. However, little is known about epigenetic signaling in glia and nothing is known about the intersection of glial epigenetic signaling and presynaptic homeostatic plasticity. During a screen for genes involved in presynaptic homeostatic synaptic plasticity, we identified an essential role for the histone acetyltransferase and deubiquitinase SAGA complex in peripheral glia. We present evidence that the SAGA complex is necessary for homeostatic plasticity, demonstrating involvement of four new genes in homeostatic plasticity. This is also evidence that glia participate in presynaptic homeostatic plasticity, invoking previously unexplored intercellular, homeostatic signaling at a tripartite synapse. We show, mechanistically, SAGA signaling regulates the composition of and signaling from the extracellular matrix during homeostatic plasticity.

中文翻译：

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神经胶质细胞的表观遗传信号控制突触前稳态可塑性。


表观遗传基因调控决定胚胎神经系统中神经元的命运。胚胎后，神经元内的表观遗传信号与学习障碍、自闭症、共济失调和精神分裂症有关。表观遗传因子也富含于神经胶质细胞中。然而，人们对神经胶质细胞的表观遗传信号知之甚少，并且对于神经胶质细胞表观遗传信号和突触前稳态可塑性的交叉点也一无所知。在筛选与突触前稳态突触可塑性相关的基因时，我们发现了组蛋白乙酰转移酶和去泛素化酶 SAGA 复合物在外周神经胶质细胞中的重要作用。我们提出证据表明 SAGA 复合体对于稳态可塑性是必需的，证明了四个新基因参与稳态可塑性。这也是神经胶质细胞参与突触前稳态可塑性的证据，在三方突触处调用先前未探索的细胞间稳态信号传导。我们表明，从机制上讲，SAGA 信号传导在稳态可塑性过程中调节细胞外基质的组成和信号传导。