TY - JOUR T1 - Differential epigenetic landscapes and transcription factors explain X-linked gene behaviours during X-chromosome reactivation in the mouse inner cell mass JF - bioRxiv DO - 10.1101/166249 SP - 166249 AU - Maud Borensztein AU - Ikuhiro Okamoto AU - Laurène Syx AU - Guillaume Guilbaud AU - Christel Picard AU - Katia Ancelin AU - Rafael Galupa AU - Patricia Diabangouaya AU - Nicolas Servant AU - Emmanuel Barillot AU - Azim Surani AU - Mitinori Saitou AU - Chong-Jian Chen AU - Konstantinos Anastassiadis AU - Edith Heard Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/21/166249.abstract N2 - X-chromosome inactivation (XCI) is established in two waves during mouse development. First, silencing of the paternal X chromosome (Xp) is triggered, with transcriptional repression of most genes and enrichment of epigenetic marks such as H3K27me3 being achieved in all cells by the early blastocyst stage. XCI is then reversed in the inner cell mass (ICM), followed by a second wave of maternal or paternal XCI, in the embryo-proper. Although the role of Xist RNA in triggering XCI is now clear, the mechanisms underlying Xp reactivation in the inner cell mass have remained enigmatic. Here we use in vivo single cell approaches (allele-specific RNAseq, nascent RNA FISH and immunofluorescence) and find that different genes show very different timing of reactivation. We observe that the genes reactivate at different stages and that initial enrichment in H3K27me3 anti-correlates with the speed of reactivation. To define whether this repressive histone mark is lost actively or passively, we investigate embryos mutant for the X-encoded H3K27me3 demethylase, UTX. Xp genes that normally reactivate slowly are retarded in their reactivation in Utx mutants, while those that reactive rapidly are unaffected. Therefore, efficient reprogramming of some X-linked genes in the inner cell mass is very rapid, indicating minimal epigenetic memory and potentially driven by transcription factors, whereas others may require active erasure of chromatin marks such as H3K27me3. ER -