Department Biochemie, Ludwig-Maximilians Universität München, Genzentrum, 81377, München, Germany.
Fakultät für Biologie, Ludwig-Maximilians Universität München, Biozentrum, 82152, Planegg-Martinsried, Germany.
Bioessays. 2020 Apr;42(4):e1900188. doi: 10.1002/bies.201900188. Epub 2020 Mar 6.
Measurements of open chromatin in specific cell types are widely used to infer the spatiotemporal activity of transcriptional enhancers. How reliable are these predictions? In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers. Instead, recent studies focusing on the quantitative nature of accessibility signal reveal subtle differences between active enhancers and their different inactive counterparts: the closed silenced state and the accessible primed and repressed states. While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states. Molecular mechanisms that may account for these quantitative differences are discussed. A model that relates molecular events at an enhancer to changes in its activity and accessibility in a developing tissue is also proposed.
测量特定细胞类型中的开放染色质广泛用于推断转录增强子的时空活性。这些预测有多可靠？在这篇综述中，有人认为，仅仅考虑开放与关闭染色质，或者活跃与非活跃增强子，不足以充分描述增强子的可及性和活性之间的关系。相反，最近的研究集中于可及性信号的定量性质，揭示了活跃增强子与其不同的非活跃对应物之间的细微差异：封闭的沉默状态，以及可及的启动和抑制状态。虽然开放结构本身并不是增强子活性的特定指标，但活跃的增强子显示出比启动和抑制状态更高的可及性。讨论了可能解释这些定量差异的分子机制。还提出了一个将增强子上的分子事件与发育组织中其活性和可及性的变化联系起来的模型。
