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

Tatsuya Ohhata, Kazuki Yamazawa, Asuka Miura-Kamio, Saori Takahashi, Satoshi Sakai, Yuka Tamura, Chiharu Uchida, Kyoko Kitagawa, Hiroyuki Niida, Ichiro Hiratani, Hisato Kobayashi, Hiroshi Kimura (+2 others)
2021 Cell Reports  
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
more » ... ep, 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.
doi:10.1016/j.celrep.2021.108912 pmid:33789104 fatcat:ev4h5zkmpjffre4s36zapgeadi