Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice

In female mammals,activation of xist (x-inactive specific transcript) is essential for establishment of x chromosome inactivation. during early embryonic development in mice,paternal xist is preferentially expressed whereas maternal xist (xm-xist) is silenced. unlike autosomal imprinted genes,xist imprinting for xm-xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. however,the molecular mechanism underlying the variable nature of xm-xist imprinting is poorly understood. here,we revealed that xm-xist silencing depends on chromatin condensation states at the xist/tsix genomic region and on rnf12 expression levels. in early preimplantation,chromatin decondensation via h3k9me3 loss and histone acetylation gain caused xm-xist derepression irrespective of embryo type. although the presence of the paternal genome during pronuclear formation impeded xm-xist derepression,xm-xist was robustly derepressed when the maternal genome was decondensed before fertilization. once xm-xist was derepressed by chromatin alterations,the derepression was stably maintained and rescued xmxpδ lethality,indicating that loss of xm-xist imprinting was irreversible. in late preimplantation,oct4 served as a chromatin opener to create transcriptional permissive states at xm-xist/tsix genomic loci. in parthenogenetic embryos,rnf12 overdose caused xm-xist derepression via xm-tsix repression; physiological rnf12 levels were essential for xm-xist silencing maintenance in fertilized embryos. thus,chromatin condensation and fine-tuning of rnf12 dosage were crucial for xist imprint maintenance by silencing xm-xist. © 2016 fukuda et al.