Genomic reorganizations mediating the engagement of target genes to transcription factories (TFs), characterized as specialized nuclear subcompartments enriched in hyperphosphorylated RNA polymerase II (RNAPII) and transcriptional regulators, act as an important layer of control in coordinating efficient gene transcription. However, their presence in hippocampal neurons and potential role in activity-dependent coregulation of genes within the brain remains unclear. Here, we investigate whether the well-characterized role for the histone acetyltransferase (HAT) Tip60 in mediating epigenetic control of inducible neuroplasticity genes involves TF associated chromatin reorganization in the hippocampus. We show that Tip60 shuttles into the nucleus following extracellular stimulation of rat hippocampal neurons with concomitant enhancement of Tip60 binding and activation of specific synaptic plasticity genes. Multicolor three-dimensional (3D) DNA fluorescent in situ hybridization (DNA-FISH) reveals that hippocampal stimulation mobilizes these same synaptic plasticity genes and Tip60 to RNAPII-rich TFs. Our data support a model by which external hippocampal stimulation promotes intracellular Tip60 HAT dynamics with concomitant TF associated genome reorganization to initiate Tip60mediated synaptic gene activation.

中文翻译：

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海马刺激通过伴随基因组重组和突触基因激活来促进细胞内Tip60动力学。

介导目标基因与转录工厂（TFs）结合的基因组重组，其特征是富含超磷酸化RNA聚合酶II（RNAPII）和转录调节因子的专门核子小室，是协调有效基因转录的重要控制层。然而，它们在海马神经元中的存在以及在脑内基因的活动依赖性基因调控中的潜在作用仍不清楚。在这里，我们调查组蛋白乙酰转移酶（HAT）Tip60在介导可诱导的神经可塑性基因的表观遗传控制中是否具有充分表征的作用，涉及海马体中与TF相关的染色质重组。我们显示，Tip60穿梭进入细胞核后，大鼠海马神经元的细胞外刺激伴随着Tip60结合增强和特定突触可塑性基因的激活。多色三维（3D）DNA荧光原位杂交（DNA-FISH）表明，海马刺激动员了这些相同的突触可塑性基因和Tip60到富含RNAPII的TF。我们的数据支持一个模型，通过该模型，外部海马刺激可促进细胞内Tip60 HAT动态，并伴随TF相关基因组重组，从而启动Tip60介导的突触基因激活。多色三维（3D）DNA荧光原位杂交（DNA-FISH）表明，海马刺激动员了这些相同的突触可塑性基因和Tip60到富含RNAPII的TF。我们的数据支持一个模型，通过该模型，外部海马刺激可促进细胞内Tip60 HAT动态，并伴随TF相关基因组重组，从而启动Tip60介导的突触基因激活。多色三维（3D）DNA荧光原位杂交（DNA-FISH）表明，海马刺激动员了这些相同的突触可塑性基因和Tip60到富含RNAPII的TF。我们的数据支持一个模型，通过该模型，外部海马刺激可促进细胞内Tip60 HAT动态，并伴随TF相关基因组重组，从而启动Tip60介导的突触基因激活。