Research
| Title： | POGZ suppresses 2C transcriptional program and retrotransposable elements |
|---|---|
| First author： | Sun, Xiaoyun; Zhang, Tianzhe; Tong, Bei; Cheng, Linxi; Jiang, Wei; Sun, Yuhua |
| Journal： | CELL REPORTS |
| Years： | 2023 |
| DOI： | 10.1016/j.celrep.2023.112867 |
| Abstract： | The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs). However, the exact mechanisms remain unclear. Here, we show that POGZ plays an important role in the maintenance of ESCs by silencing Dux and endogenous retroviruses (ERVs). POGZ maintains a silent chromatin state at Dux and ERVs by associating with and recruiting TRIM28 and SETDB1, and its loss leads to decreased levels of H3K9me3/H4K20me3, resulting in up-regulation of 2C tran-scripts and ESC transition to a 2C-like state. POGZ suppresses different classes of ERVs through direct (IAPEy, the intracisternal A-type particle elements) and indirect regulation (MERVL). Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural disease genes such as Serpina3m. Our find-ings provide important insights into understanding the disease mechanism caused by POGZ dysfunction. |
