Dynamics of transcription-mediated conversion from euchromatin to facultative heterochromatin at the Xist promoter by Tsix

The fine-scale dynamics from euchromatin (EC) to facultative heterochromatin (fHC) has remained largely unclear. Here, we focus on Xist and its silencing initiator Tsix as a paradigm of transcription-mediated conversion from EC to fHC. In mouse epiblast stem cells, induction of Tsix recapitulates the conversion at the Xist promoter. Investigating the dynamics reveals that the conversion proceeds in a stepwise manner. Initially, a transient opened chromatin structure is observed. In the second step, gene silencing is initiated and dependent on Tsix, which is reversible and accompanied by simultaneous changes in multiple histone modifications. At the last step, maintenance of silencing becomes independent of Tsix and irreversible, which correlates with occupation of the −1 position of the transcription start site by a nucleosome and initiation of DNA methylation introduction. This study highlights the hierarchy of multiple chromatin events upon stepwise gene silencing establishment. [Display omitted] •Dynamics from euchromatin to facultative heterochromatin at the Xist promoter by Tsix•Before gene silencing, a transient relaxed chromatin structure is observed•Initiation of gene silencing is accompanied by multiple histone modifications•Silencing becomes irreversible with DNA methylation and closing chromatin structure The fine-scale dynamics from euchromatin to facultative heterochromatin remains unclear. Ohhata et al. develop a cell system that allows the investigation of Tsix-regulated Xist repression dynamics in detail. They report stepwise dynamics of multiple chromatin signatures at the Xist promoter with high temporal resolution.