TY - JOUR T1 - Xist Intron 1 Repression by TALE Transcriptional Factor Improves Somatic Cell Reprogamming in Mice JF - bioRxiv DO - 10.1101/259234 SP - 259234 AU - Jindun Zhang AU - Xuefei Gao AU - Jian Yang AU - Xiaoying Fan AU - Wei Wang AU - Yanfeng Liang AU - Lihong Fan AU - Hongmei Han AU - Xiaorong Xu AU - Fuchou Tang AU - Siqin Bao AU - Pentao Liu AU - Xihe Li Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/02/02/259234.abstract N2 - Xist is the master regulator of X chromosome inactivation (XCI). In order to further understand the Xist locus in reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) and in somatic cell nuclear transfer (SCNT), we tested transcription-factor-like effectors (TALE)-based designer transcriptional factors (dTFs), which were specific to numerous regions at the Xist locus. We report that the selected dTF repressor 6 (R6) binding the intron 1 of Xist, which did not affect Xist expression in mouse embryonic fibroblasts (MEFs), substantially improved the iPSC generation and the SCNT preimplantation embryo development. Conversely, the dTF activator targeting the same genomic region of R6 decreased iPSC formation, and blocked SCNT-embryo development. These results thus uncover the critical requirement for the Xist locus in epigenetic resetting, which is not directly related to Xist transcription. This may provide a unique route to improving the reprogramming. ER -