Transcriptional dynamics of paternal X chromosome reveals different epigenetic memory of the inactive state in the inner cell mass. Mus musculus

This study concerns the dynamics of reprogramming of the inactive X chromosome in the inner cell mass of the E3.5-4.5 mouse blastocysts. We use single cell, allele-specific transcriptomic analyses to define the precise timing of paternal X-linked gene reactivation, as well as nascent RNA FISH and immunuofluorescence to follow the loss of chromatin marks such as H3K27me3. We find evidence that different genes show very different timing of reactivation indicating an epigenetic memory of the inactive state in some cases but not in others. In exploring whether PRC2 might be part of this memory we uncover a role for the X-linked histone demethylase Utx (a gene that actually escapes XCI), in the efficiency of H3K27me3 erasure and reactivation of of the paternal X. This work describes the precise timing and potential mechanisms of X-chromosome reactivation in vivo for the first time. Overall design: 40 single-cells RNAseq from mouse pre-implantation embryos.