Single-cell analysis reveals X upregulation is not global in pre-gastrulation embryos

In mammals, transcriptional inactivation of one X chromosome in female compensates for the dosage of X-linked gene expression between the sexes. Additionally, it is believed that the upregulation of active X chromosome in male and female balances the dosage of X-linked gene expression relative to autosomal genes, as proposed by Ohno. However, the existence of X chromosome upregulation (XCU) remains controversial. Here, we have profiled gene-wise dynamics of XCU in pre-gastrulation mouse embryos at single-cell level and found that XCU is dynamically linked with X chromosome inactivation (XCI); however, XCU is not global like XCI. Moreover, we show that upregulated genes are enriched with activating marks and have enhanced burst frequency. Finally, our In-silico model predicts that recruitment probabilities of activating factors and a surge of these factors upon X-inactivation trigger XCU. Altogether, our study provides significant insight into the gene-wise dynamics and mechanistic basis of XCU during early development and extends support for Ohno’s hypothesis.