Allele-specific ATAC-seq of SmcHD1 KO cell lines upon Xist induction with NPC differentiation
X chromosome inactivation (XCI) in mammals is mediated by Xist RNA which functions in cis to silence genes on a single X chromosome in XX female cells, thereby equalising levels of X-linked gene expression relative to XY males. XCI progresses over a period of several days, with some X-linked genes silencing faster than others. Chromosomal location of a gene is an important determinant of silencing rate, but uncharacterised gene-intrinsic features also mediate resistance or susceptibility to silencing. In this study, we examine mouse embryonic stem cell lines with an inducible Xist allele (iXist-ChrX mESCs) and integrate allele-specific data of gene silencing and decreasing inactive X (Xi) chromatin accessibility over time-courses of Xist induction with cellular differentiation. Our analysis reveals that motifs bound by the transcription factor YY1 are associated with persistently accessible regulatory elements, including many promoters and enhancers of slow-silencing genes. We further show that YY1 is evicted relatively slowly from target sites on Xi, and that silencing of X-linked genes is increased upon YY1 degradation. Together our results suggest that YY1 acts as barrier to Xist-mediated silencing until late stages of the XCI process. Overall design: This series contains data of ATAC-seq from time-courses of inducible XCI in iXist-ChrX mESCs comparing WT with SmcHD1 KO cell lines. The genotypes of these model cell lines are female interspecific hybrids between M.m.Domesticus and M.m.Castaneous mouse strains, with dox-inducible Xist engineered onto either the Domesticus (iXist-ChrX-Dom) or Castaneous (iXist-ChrX-Cast) allele (Nesterova et al, 2019). SmcHD1 KO clones were derived from each of these parental lines as documented in our previous publication, SmA3 from iXist-ChrX-Dom and SmD5 from iXist-ChrX-Cast (Bowness et al, 2022). Time-courses of Xist induction with differentiation from mESCs to NPCs were conducted in parallel for WT and SmcHD1 KO, and timepoints of 0, 3, 5, 7 and 15 days were taken for comparison. At later timepoints of the time-courses, more accessibility is retained at regulatory elements on the inactive X chromosome (Xi) in SmcHD1 KO compared to WT.