Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks.

中文翻译：

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增强子活性需要CBP / P300依赖溴域的组蛋白H3K27乙酰化。

赖氨酸27处的组蛋白H3的乙酰化是增强子活性的明确定义的标记。但是，这种修饰对增强子的功能影响知之甚少。在这里，我们使用化学遗传学方法在血液恶性肿瘤模型中急性阻断cAMP反应元件结合蛋白（CREB）结合蛋白（CBP）/ P300 bromodomain的功能，并描述了由此导致的H3K27Ac的特异性丧失，尽管该过程仍在继续。染色质上存在CBP / P300。使用这种方法来剖析H3K27Ac在增强子上的作用，我们确定了这种修饰在增强子RNA的生产和增强子调控的基因网络的转录中的关键作用。