POGZ suppresses 2C transcriptional program and retrotransposable elements

Xiaoyun Sun; Tianzhe Zhang; Bei Tong; Linxi Cheng; Wei Jiang; Yuhua Sun

Cell Reports (Aug 2023)

POGZ suppresses 2C transcriptional program and retrotransposable elements

Xiaoyun Sun,
Tianzhe Zhang,
Bei Tong,
Linxi Cheng,
Wei Jiang,
Yuhua Sun

Affiliations

Xiaoyun Sun: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China
Tianzhe Zhang: Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China
Bei Tong: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China
Linxi Cheng: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China
Wei Jiang: Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China
Yuhua Sun: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan 430072, P.R. China; Hubei Hongshan Laboratory, Wuhan 430070, P.R. China; Corresponding author

Journal volume & issue: Vol. 42, no. 8
p. 112867

Abstract

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Summary: 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 transcripts 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 findings provide important insights into understanding the disease mechanism caused by POGZ dysfunction.

CP: Developmental biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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