In mammals, dosage compensation involves two parallel processes: (1) X inactivation, which equalizes X chromosome dosage between males and females, and (2) X hyperactivation, which upregulates the active X for X-autosome balance. The field currently favors models whereby dosage compensation initiates “de novo” during mouse development. Here, we develop “So-Smart-seq” to revisit the question and interrogate a comprehensive transcriptome including noncoding genes and repeats in mice. Intriguingly, de novo silencing pertains only to a subset of Xp genes. Evolutionarily older genes and repetitive elements demonstrate constitutive Xp silencing, adopt distinct signatures, and do not require Xist to initiate silencing. We trace Xp silencing backward in developmental time to meiotic sex chromosome inactivation in the male germ line and observe that Xm hyperactivation is timed to Xp silencing on a gene-by-gene basis. Thus, during the gamete-to-embryo transition, older Xp genes are transmitted in a “pre-inactivated” state. These findings have implications for the evolution of imprinting.

在哺乳动物中，剂量补偿涉及两个平行过程：(1) X 失活，使雄性和雌性之间的 X 染色体剂量相等；(2) X 过度激活，上调活跃 X 以实现 X 常染色体平衡。该领域目前青睐在小鼠发育过程中剂量补偿启动“从头”的模型。在这里，我们开发了“So-Smart-seq”来重新审视这个问题并询问包括非编码基因和小鼠重复序列在内的全面转录组。有趣的是，从头沉默仅涉及 Xp 基因的一个子集。进化较老的基因和重复元件表现出组成型 Xp 沉默，采用不同的特征，并且不需要Xist启动沉默。我们将发育时间中的 Xp 沉默追溯到雄性种系中减数分裂性染色体失活，并观察到 ​​Xm 过度激活与 Xp 沉默在逐个基因的基础上同步。因此，在配子到胚胎的转变过程中，较旧的 Xp 基因以“失活前”状态传递。这些发现对印记的进化具有重要意义。