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

• Published in: iScience 2022-06, Vol.25 (6), p.104465-104465, Article 104465
• Main Authors: Naik, Hemant Chandru, Hari, Kishore, Chandel, Deepshikha, Jolly, Mohit Kumar, Gayen, Srimonta
• Format: Article
• Language: English
• Subjects: Bioinformatics; Biological sciences; Cell biology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104465

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. [Display omitted] •X-upregulation coincides with X chromosome inactivation in pre-gastrulation embryos•X-upregulation is not chromosome-wide like X-inactivation•Upregulated genes have enhanced burst frequency and are enriched with activating marks•A surge of activating factors on X-inactivation triggers X-upregulation Biological sciences; Molecular biology; Cell biology; Bioinformatics