Laboratory for Developmental Epigenetics, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.
Dev Growth Differ. 2021 Jan;63(1):5-17. doi: 10.1111/dgd.12709. Epub 2021 Feb 3.
During embryogenesis in mammals, the 3-dimensional (3D) genome organization changes globally in parallel with transcription changes in a cell-type specific manner. This involves the progressive formation of heterochromatin, the best example of which is the inactive X chromosome (Xi) in females, originally discovered as a compact 3D structure at the nuclear periphery known as the Barr body. The heterochromatin formation on the autosomes and the Xi is tightly associated with the differentiation state and the developmental potential of cells, making it an ideal readout of the cellular epigenetic state. At a glance, the heterochromatin appears to be uniform. However, recent studies are beginning to reveal a more complex picture, with multiple hierarchical levels co-existing within the heterochromatin compartment. Such hierarchical levels appear to exist in the heterochromatin compartment on autosomes as well as on the Xi. Here, we review recent progress in our understanding of the 3D genome organization changes during the period of differentiation surrounding pluripotency in vivo and in vitro, with a focus on the heterochromatin compartment. We first look at the whole genome, then focus on the Xi, and discuss their differences and similarities. Finally, we present a unified view of how the heterochromatin compartment is formed and regulated during early development. In particular, we emphasize that there are multiple layers within the heterochromatic compartment on both the autosomes and the Xi, with regulatory mechanisms common and specific to each layer.
在哺乳动物的胚胎发生过程中，三维（3D）基因组组织以细胞类型特异性的方式与转录变化平行地全局改变。这涉及异染色质的渐进形成，其最好的例子是女性中的失活 X 染色体（Xi），最初被发现为核周界的一种紧密的 3D 结构，称为巴氏小体。常染色体和 Xi 上的异染色质形成与细胞的分化状态和发育潜力密切相关，使其成为细胞表观遗传状态的理想读数。乍一看，异染色质似乎是均匀的。然而，最近的研究开始揭示出更复杂的情况，即在异染色质隔室中存在多个层次的共存。这种层次似乎存在于常染色体上的异染色质隔室以及 Xi 上。在这里，我们回顾了最近在理解体内和体外多能性分化过程中 3D 基因组组织变化方面的进展，重点关注异染色质隔室。我们首先看整个基因组，然后聚焦于 Xi，并讨论它们的异同。最后，我们提出了一个统一的观点，即异染色质隔室如何在早期发育过程中形成和调控。特别是，我们强调在常染色体和 Xi 上的异染色质隔室中都有多个层次，每个层次都有共同和特定的调控机制。
