Abstract：
Precise temporal and sequential control of gene expression during development and in response to environmental stimuli requires tight regulation of the physical contact between gene regulatory elements and promoters. Current models describing how the genome folds in 3D space to establish these interactions often ignore the role of the most stable structural nuclear feature - the nuclear envelope. While contributions of 3D folding within/between topologically associated domains (TADs) have been extensively described, mechanical contributions from the nuclear envelope can impact enhancer-promoter interactions both directly and indirectly through influencing intra/inter-TAD interactions. Importantly, these nuclear envelope contributions clearly link this mechanism to development and, when defective, to human disease. Here, we discuss evidence for nuclear envelope regulation of tissue-specific enhancer-promoter pairings, potential mechanisms for this regulation, exciting recent findings that other regulatory elements such as microRNAs and long noncoding RNAs are under nuclear envelope regulation, the possible involvement of condensates, and how disruption of this regulation can lead to disease.
摘要：
在发育过程中和对环境刺激的反应中，基因表达的精确时间和顺序控制需要严格调节基因调节元件和启动子之间的物理接触。目前描述基因组如何在3D空间中折叠以建立这些相互作用的模型通常忽略了最稳定的结构核特征-核包膜的作用。虽然已经广泛描述了拓扑关联域（TAD）内/之间的3D折叠的贡献，来自核膜的机械贡献可以通过影响TAD内/间相互作用直接和间接地影响增强子-启动子相互作用。重要的是,这些核包络贡献清楚地将这一机制与发展联系起来，有缺陷时，人类疾病。这里,我们讨论了组织特异性增强子-启动子配对的核包膜调节的证据，这种监管的潜在机制，令人兴奋的最新发现，其他调控元件，如microRNAs和长链非编码RNAs，冷凝物的可能参与，以及这种调节的破坏如何导致疾病。
