m6A RNA methylation in the maintenance of X-chromosome inactivation and X to autosome dosage compensation in early embryogenesis [RNA-Seq]

In females, inactivation of one X-chromosome balances the dosage of X-linked genes similar to males. In addition, transcriptional upregulation balances the dosage of genes expressed from the single active-X to the double copy of autosomes in both sexes. However, the factors and mechanisms involved in the maintenance of X-chromosome inactivation (XCI) and X to autosome dosage compensation remain poorly understood. In this study, we report the contribution of m6A RNA methylation in maintenance of XCI and X to autosome dosage compensation in early embryonic and extraembryonic lineages. In the study, we find that m6A RNA methylation has a minimal role to play in maintenance of silencing of the inactivated-X chromsoome in TSC, XEN and EpiSC . Moreover, we also show that the X-linked transcripts are less enriched with m6A than the autosomal transcripts suggesting its role in increased X-transcript stability and hence upregulation. In addition, surprisingly we observed that X-linked transcripts without m6A are fully dosage compensated than the transcripts with m6A which undergo partial X to autosome dosage compensation in TSC, XEN and EpiSC. Further, we also found that global depletion of m6A level in TSC, XEN and EpiSC has a minor effect on the X to autosome dosage balance implicating the minor contribution of m6A RNA methylation during early embryogenesis.