Spatiotemporal gene regulation is essential for accurate development and involves promoters and distal regulatory elements (DREs), such as enhancers or silencers. However, physical contacts with promoters do not always result in gene expression and how DREs contribute to gene activation is not fully understood. Mahara et al. combine chromatin conformation capture techniques with transcription and chromatin profiling during the differentiation of mouse embryonic stem cells into neural progenitor cells to identify chromatin topologies that contribute to gene induction. They observe distinct genome topologies, as well as transient interactions, with high topological remodeling associated with a higher magnitude of transcriptional induction. Interestingly, both the acquisition of physical contacts between DREs and gene promoters and their loss and transient formation are associated with transcriptional dynamics during differentiation. In this context, preventing the formation and disruption of transient interactions impairs early gene activation, pointing to an important role of dynamic chromatin topologies in the early stages of development. This work highlights the importance of temporal promoter interactions in modulating the induction of gene expression programs required for proper development.

Original reference: Mol. Cell https://doi.org/10.1016/j.molcel.2024.10.005 (2024)

时空基因调控对于准确发育至关重要，涉及启动子和远端调节元件 （DRE），例如增强子或沉默子。然而，与启动子的物理接触并不总是导致基因表达，并且 DRE 如何促进基因激活尚不完全清楚。Mahara 等人在小鼠胚胎干细胞分化为神经祖细胞的过程中将染色质构象捕获技术与转录和染色质分析相结合，以鉴定有助于基因诱导的染色质拓扑结构。他们观察到不同的基因组拓扑结构以及瞬时相互作用，其中高度拓扑重塑与较高幅度的转录诱导相关。有趣的是，DREs 和基因启动子之间物理接触的获得以及它们的丢失和瞬时形成都与分化过程中的转录动力学有关。在这种情况下，阻止瞬时相互作用的形成和破坏会损害早期基因激活，这表明动态染色质拓扑结构在发育的早期阶段起着重要作用。这项工作强调了时间启动子相互作用在调节正常发育所需的基因表达程序诱导中的重要性。

Original reference: Mol. Cell https://doi.org/10.1016/j.molcel.2024.10.005 (2024)