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성균관대학교 의과대학

Proc. Natl. Acad. Sci. USA, First published November 20, 2019 | https://doi.org/10.1073/pnas.1916306116 Roles of ErbB3 binding protein 1 (EBP1) in embryonic development and gene-silencing control

Hyo Rim Ko^a,b, Inwoo Hwang^a,b, Eun-Ju Jin^a,b, Taegwan Yun^a,b, Dongryeol Ryu^a, Jong-Sun Kang^a,b,c, Kye Won Park^d, Joo-Ho Shin^a,b,c, Sung-Woo Cho^e, Kyung-Hoon Lee^b,f, Keqiang Ye^g, and Jee-Yin Ahn^a,b,c,1

^aDepartment of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 16419 Suwon, Korea; ^bSingle Cell Network Research Center, Sungkyunkwan University School of Medicine, 16419 Suwon, Korea; ^cSamsung Biomedical Research Institute, Samsung Medical Center, 06351 Seoul, Korea;
^dDepartment of Food Science and Biotechnology, Sungkyunkwan University, 16419 Suwon, Korea; ^eDepartment of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, 05505 Seoul, Korea; ^fDepartment of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea; and ^gDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322

¹To whom correspondence may be addressed.

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; Ebp1flox/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.

Ebp1, epigenetic control, transcriptional repression, DNA methylation, cell death

논문정보

형식Research article
게재일2019년 11월 (BRIC 등록일 2019-11-26)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학

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