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CBP/p300 inhibitor C646 prevents high glucose exposure induced neuroepithelial cell proliferation
Author(s) -
Bai Baoling,
Zhang Qin,
Wan Chunlei,
Li Dan,
Zhang Ting,
Li Huili
Publication year - 2018
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1360
Subject(s) - neuroepithelial cell , histone acetyltransferase , acetylation , biology , microbiology and biotechnology , histone h4 , epigenetics , neural tube , neural stem cell , biochemistry , embryo , stem cell , gene
Background Maternal diabetes related neural tube defects (NTDs) are a result of oxidative stress and apoptosis. However, the molecular mechanism behind the pathogenesis is not fully understood. Here, we report that high glucose exposure‐induced epigenetic changes influence histone H4 acetylation and neuroepithelial cell proliferation. We also show that the acetyltransferase inhibitor C646 can prevent high glucose induced changes in histone H4 acetylation and neuroepithelial cell proliferation. Methods By using LC‐MS/MS as an unbiased approach, we screened the histone acetylation profile in an E9 neuroepithelial cell line (NE‐4C) under high glucose exposure. We further explored the mechanism in cells in vitro and in maternal diabetes‐induced mouse embryos in vivo . Results We identified 35 core histone acetylation marks in normal E9 neuroepithelial cells, whereas high glucose exposure resulted in novel acetylation sites on H4K31 and H4K44. Acetylation levels of embryonic development associated H4K5/K8/K12/K16 increased in neuroepithelial cells exposed to high glucose in vitro and in brain tissue from maternal diabetes induced exencephalic embryos in vivo . Further, mRNA level of histone acetyltransferase CBP encoded gene Crebbp was significantly increased both in vitro and in vivo . The addition of C646, a selective inhibitor for CBP/p300, significantly rescued increase of H4K5/K8/K12/K16 acetylation levels and H3S10pi‐labeled neuroepithelial cell proliferation induced by high glucose exposure. Conclusion Our data provide complementary insights for potential mechanisms of maternal diabetes induced NTDs.