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Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control.


ABSTRACT: ErbB3-binding protein 1 (EBP1) is implicated in diverse cellular functions, including apoptosis, cell proliferation, and differentiation. Here, by generating genetic inactivation of Ebp1 mice, we identified the physiological roles of EBP1 in vivo. Loss of Ebp1 in mice caused aberrant organogenesis, including brain malformation, and death between E13.5 and 15.5 owing to severe hemorrhages, with massive apoptosis and cessation of cell proliferation. Specific ablation of Ebp1 in neurons caused structural abnormalities of brain with neuron loss in [Nestin-Cre; Ebp1 flox/flox ] mice. Notably, global methylation increased with high levels of the gene-silencing unit Suv39H1/DNMT1 in Ebp1-deficient mice. EBP1 repressed the transcription of Dnmt1 by binding to its promoter region and interrupted DNMT1-mediated methylation at its target gene, Survivin promoter region. Reinstatement of EBP1 into embryo brain relived gene repression and rescued neuron death. Our findings uncover an essential role for EBP1 in embryonic development and implicate its function in transcriptional regulation.

SUBMITTER: Ko HR 

PROVIDER: S-EPMC6900500 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control.

Ko Hyo Rim HR   Hwang Inwoo I   Jin Eun-Ju EJ   Yun Taegwan T   Ryu Dongryeol D   Kang Jong-Sun JS   Park Kye Won KW   Shin Joo-Ho JH   Cho Sung-Woo SW   Lee Kyung-Hoon KH   Ye Keqiang K   Ahn Jee-Yin JY  

Proceedings of the National Academy of Sciences of the United States of America 20191120 49


ErbB3-binding protein 1 (EBP1) is implicated in diverse cellular functions, including apoptosis, cell proliferation, and differentiation. Here, by generating genetic inactivation of <i>Ebp1</i> mice, we identified the physiological roles of EBP1 in vivo. Loss of <i>Ebp1</i> in mice caused aberrant organogenesis, including brain malformation, and death between E13.5 and 15.5 owing to severe hemorrhages, with massive apoptosis and cessation of cell proliferation. Specific ablation of Ebp1 in neuro  ...[more]

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