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Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/β‐catenin pathway in mice
Author(s) -
Li Nan,
Kong Ming,
Zeng Sheng,
Hao Chenzhi,
Li Min,
Li Luyang,
Xu Zheng,
Zhu Min,
Xu Yong
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800197r
Subject(s) - liver regeneration , wnt signaling pathway , chromatin remodeling , hepatocyte , regeneration (biology) , demethylase , microbiology and biotechnology , knockout mouse , catenin , beta catenin , chromatin , gene , biology , chemistry , epigenetics , signal transduction , genetics , in vitro
Liver regeneration is a complicated pathophysiologic process that is regulated by a myriad of signaling pathways and transcription factors. The interaction among these pathways and factors, either cooperatively or antagonistically, may ultimately lead to recovery and restoration of liver function or permanent loss of liver function and liver failure. In the present study, we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates liver regeneration in mice. The Smarca4 ‐Flox strain of mice was crossbred with the Alb‐ Cre strain to generate hepatocyte‐specific Brg1 knockout mice. Liver injury was induced by partial hepatectomy (PHx). We report that Brg1 deletion in hepatocyte compromised liver regeneration and dampened survival after PHx in mice. Brg1 interacted with β‐catenin to potentiate Wnt signaling and promote hepatocyte proliferation. Mechanistically, Brg1 recruited lysine demethylase 4 (KDM4) to activate β‐catenin target genes. Our data suggest that Brg1 might play an essential role maintaining hepatic homeostasis and contributing to liver repair.—Li, N., Kong, M., Zeng, S., Hao, C., Li, M., Li, L., Xu, Z., Zhu, M., Xu, Y. Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/β‐catenin pathway in mice. FASEB J. 33, 327–338 (2019). www.fasebj.org