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Cantone Reversal of X chromosome inactivation

A

B

C

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
[62]
naïve (XaXa XIST-expressing) state . 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
Journal of Translational Genetics and Genomics ¦ Volume 1 ¦ November 16, 2017 7