fig2

Figure 2. Human Xi reactivation in pluripotent cells. Schematic representation of epigenetic changes that are associated with Xi reactivation in different model systems. (A) Erosion of XCI in primed human pluripotent cells (i.e., ESCs and iPSCs) leads to partial Xi gene reactivation that leads to the "eroded" X chromosome (Xe). Sequential Xi chromatin changes occur ahead of gene reactivation and include XACT re-expression and Xi localization followed by loss of Xi-associated XIST and H3K27me3^[107]. The extent of Xi reactivation and the reactivated genes vary in different cell lines. Xi genes that are refractory to erosion (i.e., HUWE1 and ATRX) remain mono-allelically expressed; (B) reprogramming of primed human pluripotent cells to the naïve state is represented accordingly to 5iLAF^[116]. XIST expression and its enrichment on the human Xi (i.e., Xi-associated XIST) are transiently lost during the transition from the primed (XaXi XIST-expressing) to naïve (XaXa XIST-expressing) state^[62]. No data is available for H3K27me3 enrichment on the Xi neither for XACT relative to the timing of transient XIST loss (highlighted by question marks); (C) reprogramming of human somatic cells by fusion with mouse ESCs induces partial Xi gene reactivation (Xa*) ahead of cell division^[126]. In this system, loss of H3K27me3 enrichment and XIST delocalization from the Xi are early chromatin changes that precede Xi gene reactivation. Importantly Xi genes that are refractory to erosion show bi-allelic expression in the subset of cells where XIST is delocalized. XACT re-expression is a later event and is not associated with Xi gene reactivation. XCI: X chromosome inactivation; Xi: inactive X chromosome; Xa: active X chromosome; Xp: paternal X chromosome; PSC: pluripotent stem cell; ESC: embryonic stem cell