XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors.

XIST（X 失活特异性转录物）长链非编码 RNA （lncRNA） 负责胎盘哺乳动物的 X 染色体失活 （XCI），但它在人类女性植入前胚胎的两条 X 染色体上积累，而不会触发 X 染色体沉默。XACT（X 活性涂层转录物）lncRNA 与活性 X 染色体上的 XIST 共积累，并可能拮抗 XIST 功能。在这里，我们使用处于多能性幼稚状态的人类胚胎干细胞来评估 XIST 和 XACT 在植入前发育过程中塑造 X 染色体染色质和转录景观中的功能。我们表明 XIST 触发多梳介导的抑制组蛋白修饰的沉积，并以 SPEN 依赖性方式抑制大多数 X 连锁基因的转录，而 XACT 缺陷不会显着影响 XIST 活性或 X 连锁基因表达。我们的研究表明，XIST 在 XCI 之前起作用，证实了 X 染色体剂量补偿的瞬态过程的存在，并揭示了 XCI 和阻尼依赖于同一组因素。