Abstract：
Neuronal activity-dependent transcription plays a key role in plasticity and pathology in the brain. An intriguing question is how neuronal activity controls gene expression via interactions of transcription factors with DNA and chromatin modifiers in the nucleus. By utilizing single-molecule imaging in human embryonic stem cell (ESC)-derived cortical neurons, we demonstrate that neuronal activity increases repetitive emergence of cAMP response element-binding protein (CREB) at histone acetylation sites in the nucleus, where RNA polymerase II (RNAPII) accumulation and FOS expression occur rapidly. Neuronal activity also enhances co-localization of CREB and CREB-binding protein (CBP). Increased binding of a constitutively active CREB to CBP efficiently induces CREB repetitive emergence. On the other hand, the formation of histone acetylation sites is dependent on CBP histone modification via acetyltransferase (HAT) activity but is not affected by neuronal activity. Taken together, our results suggest that neuronal activity promotes repetitive CREB-CRE and CREB-CBP interactions at predetermined histone acetylation sites, leading to rapid gene expression.
摘要：
神经元活性依赖性转录在大脑的可塑性和病理学中起关键作用。一个有趣的问题是神经元活性如何通过转录因子与细胞核中DNA和染色质修饰剂的相互作用来控制基因表达。通过在人类胚胎干细胞（ESC）来源的皮质神经元中利用单分子成像，我们证明，神经元活性增加了cAMP反应元件结合蛋白（CREB）在细胞核中组蛋白乙酰化位点的重复出现，其中RNA聚合酶II（RNAPII）积累和FOS表达迅速发生。神经元活性还增强CREB和CREB结合蛋白(CBP)的共定位。组成型活性CREB与CBP的结合增加有效地诱导CREB重复出现。另一方面,组蛋白乙酰化位点的形成取决于通过乙酰转移酶（HAT）活性进行的CBP组蛋白修饰，但不受神经元活性的影响。一起来看,我们的结果表明，神经元活动促进重复CREB-CRE和CREB-CBP相互作用在预定的组蛋白乙酰化位点，导致基因快速表达。
