YY1 ChIP-seq (T7 Ab) over a time course of Xist induction and NPC differentiation in iXist-ChrX YY1-FKBP-T7 cell lines
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 from ChIP-seq experiments performed in iXist-ChrX YY1-FKBP12-3xT7 cells over a time course of Xist induction with mESC to NPC differentiation. ChIP-seq was performed with an antibody raised against the T7 tag, which generates data of superior signal:noise than endogenous YY1 antibodies. Timecourses of 0, 3, 5, 7 and NPC (d18 or d28) were performed for each of two biological replicate YY1-FKBP12-3xT7 clones, aF1 and cC3. Clone aF1 derives from the iXist-ChrX-Dom line, so inducible Xist silences from the the Domesticus/129/Sv allele and only ChrX sequence proximal to the Xist locus (0-103Mb) is amenable to allelic analysis. Clone cC3 derives from the iXist-ChrX-Cast line, so inducible Xist is on the reciprocal Castaneous allele and the whole chromosome can be analysed allelically. The series also contains YY1 ChIP from aF1 and cC3 mESCs with 6 days of Xist induction but no NPC differentiation, which show considerably more remaining YY1 binding on Xi than samples with differentiation.