Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration
| Autor: | Hao Zhu, Jen Chieh Chuang, Shuyuan Zhang, Meng Wu, Zhong Wang, Liem H. Nguyen, Jian Xu, Linwei Wu, Chao Xing, Lin Li, Robert A.J. Signer, Yong Zhao, Thomas Maples, Yi Chun Kuo, Mahsa Sorouri, Xin Liu, Sam C. Wang, Ibrahim Nassour, Cemre Celen, Mohammed Kanchwala, Hanquan Liang, Xuxu Sun |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
ARID1A Cellular differentiation Mice Transgenic Biology Article Mice 03 medical and health sciences Fibrosis Genetics medicine Animals E2F4 Cell Proliferation Regeneration (biology) Nuclear Proteins Cell Differentiation Cell Biology medicine.disease SWI/SNF Liver regeneration Liver Regeneration DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology Liver Commentary Cancer research Molecular Medicine Reprogramming Transcription Factors |
| Zdroj: | Cell Stem Cell. 18:456-466 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2016.03.001 |
| Popis: | Mammals have partially lost the extensive regenerative capabilities of some vertebrates, possibly as a result of chromatin-remodeling mechanisms that enforce terminal differentiation. Here, we show that deleting the SWI/SNF component Arid1a substantially improves mammalian regeneration. Arid1a expression is suppressed in regenerating tissues, and genetic deletion of Arid1a increases tissue repair following an array of injuries. Arid1a deficiency in the liver increases proliferation, reduces tissue damage and fibrosis, and improves organ function following surgical resection and chemical injuries. Hepatocyte-specific deletion is also sufficient to increase proliferation and regeneration without excessive overgrowth, and global Arid1a disruption potentiates soft tissue healing in the ear. We show that Arid1a loss reprograms chromatin to restrict promoter access by transcription factors such as C/ebpα, which enforces differentiation, and E2F4, which suppresses cell-cycle re-entry. Thus, epigenetic reprogramming mediated by deletion of a single gene improves mammalian regeneration and suggests strategies to promote tissue repair after injury. |
| Databáze: | OpenAIRE |
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