Directors' Research, European Molecular Biology Laboratory, Heidelberg, Germany.
Collège de France, Paris, France.
Nat Rev Mol Cell Biol. 2022 Apr;23(4):231-249. doi: 10.1038/s41580-021-00438-7. Epub 2022 Jan 10.
X-chromosome inactivation (XCI) is the epigenetic mechanism that ensures X-linked dosage compensation between cells of females (XX karyotype) and males (XY). XCI is essential for female embryos to survive through development and requires the accurate spatiotemporal regulation of many different factors to achieve remarkable chromosome-wide gene silencing. As a result of XCI, the active and inactive X chromosomes are functionally and structurally different, with the inactive X chromosome undergoing a major conformational reorganization within the nucleus. In this Review, we discuss the multiple layers of genetic and epigenetic regulation that underlie initiation of XCI during development and then maintain it throughout life, in light of the most recent findings in this rapidly advancing field. We discuss exciting new insights into the regulation of X inactive-specific transcript (XIST), the trigger and master regulator of XCI, and into the mechanisms and dynamics that underlie the silencing of nearly all X-linked genes. Finally, given the increasing interest in understanding the impact of chromosome organization on gene regulation, we provide an overview of the factors that are thought to reshape the 3D structure of the inactive X chromosome and of the relevance of such structural changes for XCI establishment and maintenance.
X 染色体失活（XCI）是一种表观遗传机制，可确保女性（XX 核型）和男性（XY）细胞之间的 X 连锁剂量补偿。XCI 对于雌性胚胎在发育过程中存活至关重要，需要许多不同因素的精确时空调节才能实现显著的全染色体基因沉默。由于 XCI，活性和非活性 X 染色体在功能和结构上是不同的，非活性 X 染色体在核内经历主要的构象重排。在这篇综述中，我们根据该快速发展领域的最新发现，讨论了启动发育过程中 XCI 并在整个生命周期中维持 XCI 所需的遗传和表观遗传调控的多个层次。我们讨论了关于 X 失活特异性转录物（XIST）调控的令人兴奋的新见解，XIST 是 XCI 的触发因子和主要调节剂，以及沉默几乎所有 X 连锁基因的机制和动力学。最后，鉴于人们越来越感兴趣地了解染色体组织对基因调控的影响，我们概述了那些被认为重塑失活 X 染色体三维结构的因素，以及这种结构变化对于 XCI 建立和维持的相关性。
